umu.sePublikasjoner
Endre søk
Begrens søket
1 - 26 of 26
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1. Abdulla, Maysaa
    et al.
    Hollander, Peter
    Pandzic, Tatjana
    Mansouri, Larry
    Ednersson, Susanne Bram
    Andersson, Per-Ola
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Fors, Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Petersen, Helga Munch
    Asmar, Fazila
    Gronbaek, Kirsten
    Enblad, Gunilla
    Cavelier, Lucia
    Rosenquist, Richard
    Amini, Rose-Marie
    Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma2020Inngår i: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 95, nr 1, s. 57-67Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.

    Fulltekst (pdf)
    fulltext
  • 2.
    Andersson-Evelönn, Emma
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Vidman, Linda
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Källberg, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik. Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Liu, Xijia
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Rydén, Patrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Combining epigenetic and clinicopathological variables improves prognostic prediction in clear cell Renal Cell CarcinomaManuskript (preprint) (Annet vitenskapelig)
  • 3.
    Borssén, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Haider, Zahra
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Norén-Nyström, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Schmiegelow, Kjeld
    Åsberg, Ann E.
    Kanerva, Jukka
    Madsen, Hans O.
    Marquart, Hanne
    Heyman, Mats
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Department of Paediatrics, University Hospital of Trondheim, Norway.
    DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia2016Inngår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 63, nr 7, s. 1185-1192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making.

    Fulltekst (pdf)
    fulltext
  • 4.
    Borssén, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nordlund, Jessica
    Haider, Zahra
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Larsson, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Kanerva, Jukka
    Schmiegelow, Kjeld
    Flaegstad, Trond
    Jónsson, Ólafur Gísli
    Frost, Britt-Marie
    Palle, Josefine
    Forestier, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Heyman, Mats
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lönnerholm, Gudmar
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia2018Inngår i: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, artikkel-id 31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients.

    Methods: Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1-18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data.

    Results: Among the 137 patients that later relapsed, patients with a CIMP-profile (n = 42) at initial diagnosis had an inferior overall survival (pOS(5years) 33%) compared to CIMP+ patients (n = 95, pOS(5years) 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors.

    Conclusion: CIMP classification is a strong candidate for improved risk stratification of relapsed BCP-ALL.

    Fulltekst (pdf)
    fulltext
  • 5.
    Degerman, Sofie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wennstedt, Sigrid
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Haider, Zahra
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Maintained memory in aging is associated with young epigenetic age2017Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 55, s. 167-171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age - chronological age) was calculated in blood samples at baseline (age: 55-65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden. A lower delta DNAm age was observed for those with maintained memory functions compared with those with average (p = 0.035) or accelerated decline (p = 0.037). Moreover, separate analyses revealed that DNAm age at follow-up, but not chronologic age, was a significant predictor of dementia (p = 0.019). Our findings suggest that young epigenetic age contributes to maintained memory in aging.

    Fulltekst (pdf)
    fulltext
  • 6.
    Forsberg, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jonsson, P Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Bergemalm, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Graffmo, Karin S
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jacobsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Rosquist, Roland
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients2010Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 7, s. e11552-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutations in CuZn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) and are found in 6% of ALS patients. Non-native and aggregation-prone forms of mutant SOD1s are thought to trigger the disease. Two sets of novel antibodies, raised in rabbits and chicken, against peptides spaced along the human SOD1 sequence, were by enzyme-linked immunosorbent assay and an immunocapture method shown to be specific for denatured SOD1. These were used to examine SOD1 in spinal cords of ALS patients lacking mutations in the enzyme. Small granular SOD1-immunoreactive inclusions were found in spinal motoneurons of all 37 sporadic and familial ALS patients studied, but only sparsely in 3 of 28 neurodegenerative and 2 of 19 non-neurological control patients. The granular inclusions were by confocal microscopy found to partly colocalize with markers for lysosomes but not with inclusions containing TAR DNA binding protein-43, ubiquitin or markers for endoplasmic reticulum, autophagosomes or mitochondria. Granular inclusions were also found in carriers of SOD1 mutations and in spinobulbar muscular atrophy (SBMA) patients and they were the major type of inclusion detected in ALS patients homozygous for the wild type-like D90A mutation. The findings suggest that SOD1 may be involved in ALS pathogenesis in patients lacking mutations in the enzyme.

    Fulltekst (pdf)
    fulltext
  • 7. Glimelius, Bengt
    et al.
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Enblad, Gunilla
    Alafuzoff, Irina
    Beskow, Anna
    Ahlström, Håkan
    Bill-Axelson, Anna
    Birgisson, Helgi
    Björ, Ove
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Edqvist, Per-Henrik
    Hansson, Tony
    Helleday, Thomas
    Hellman, Per
    Henriksson, Kerstin
    Hesselager, Göran
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Häggman, Michael
    Höglund, Martin
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Larsson, Chatarina
    Lindman, Henrik
    Ljuslinder, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Mindus, Stephanie
    Nygren, Peter
    Pontén, Fredrik
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rosenquist, Richard
    Sandin, Fredrik
    Schwenk, Jochen M.
    Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stålberg, Karin
    Stålberg, Peter
    Sundström, Christer
    Thellenberg Karlsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Westermark, Bengt
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Claesson-Welsh, Lena
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Sjöblom, Tobias
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 2, s. 187-194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umea Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

    Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

    Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

    Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

    Fulltekst (pdf)
    fulltext
  • 8.
    Grabowski, Pawel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Karlsson, Karin
    Tobin, Gerard
    Aleskog, Anna
    Thunberg, Ulf
    Laurell, Anna
    Sundström, Christer
    Rosenquist, Richard
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status2005Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 105, nr 12, s. 4807-4812Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin VH genes have better outcome than unmutated cases. VH-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, VH gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the VH-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining VH mutation status and telomere length, an improved subclassification of CLL was achieved identifying previously unrecognized patient groups with different outcomes.

  • 9.
    Haider, Zahra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Noren-Nyström, Ulrika
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Epigenetic and genetic distinctions between T-cell acute lymphoblastic leukemia and lymphomaManuskript (preprint) (Annet vitenskapelig)
  • 10.
    Haider, Zahra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Larsson, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Köhn, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Schmiegelow, Kjeld
    Flaegstad, Trond
    Kanerva, Jukka
    Heyman, Mats
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    An integrated transcriptome analysis in T-cell acute lymphoblastic leukemia links DNA methylation subgroups to dysregulated TAL1 and ANTP homeobox gene expression2019Inngår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, nr 1, s. 311-324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Classification of pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T‐ALL patients were characterized by genome‐wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P < 0.001) and mitotic age (P < 0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2‐1, and novel genes in T‐ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP− subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL‐TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP−), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.

    Fulltekst (pdf)
    fulltext
  • 11. Henckel, Ewa
    et al.
    Landfors, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Haider, Zahra
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Kosma, Paraskevi
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bohlin, Kajsa
    Hematopoietic cellular aging is not accelerated during the first 2 years of life in children born preterm2020Inngår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Prematurity in itself and exposure to neonatal intensive care triggers inflammatory processes and oxidative stress, leading to risk for disease later in life. The effects on cellular aging processes are incompletely understood.

    Methods: Relative telomere length (RTL) was measured by qPCR in this longitudinal cohort study with blood samples taken at birth and at 2 years of age from 60 children (16 preterm and 44 term). Viral respiratory infections the first year were evaluated. Epigenetic biological DNA methylation (DNAm) age was predicted based on methylation array data in 23 children (11 preterm and 12 term). RTL change/year and DNAm age change/year was compared in preterm and term during the 2 first years of life.

    Results: Preterm infants had longer telomeres than term born at birth and at 2 years of age, but no difference in telomere attrition rate could be detected. Predicted epigenetic DNAm age was younger in preterm infants, but rate of DNAm aging was similar in both groups.

    Conclusions: Despite early exposure to risk factors for accelerated cellular aging, children born preterm exhibited preserved telomeres. Stress during the neonatal intensive care period did not reflect accelerated epigenetic DNAm aging. Early-life aging was not explained by preterm birth.

    Impact: Preterm birth is associated with elevated disease risk later in life. Preterm children often suffer from inflammation early in life. Stress-related telomere erosion during neonatal intensive care has been proposed. Inflammation-accelerated biological aging in preterm is unknown. We find no accelerated aging due to prematurity or infections during the first 2 years of life.

  • 12.
    Hultdin, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Grönlund, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Eriksson-Lindström, E
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Just, T
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Telomere analysis by fluorescence in situ hybridization and flow cytometry1998Inngår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 26, nr 16, s. 3651-3656Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Determination of telomere length is traditionally performed by Southern blotting and densitometry, giving a mean telomere restriction fragment (TRF) value for the total cell population studied. Fluorescence in situ hybridization (FISH) of telomere repeats has been used to calculate telomere length, a method called quantitative (Q)-FISH, We here present a quantitative flow cytometric approach, Q-FISHFCM, for evaluation of telomere length distribution in individual cells based on in situ hybridization using a fluorescein-labeled peptide nucleic acid (PNA) (CCCTAA)(3) probe and DMA staining with propidium iodide, A simple and rapid protocol with results within 30 h was developed giving high reproducibility, One important feature of the protocol was the use of an internal cell line control, giving an automatic compensation for potential differences in the hybridization steps. This protocol was tested successfully on cell lines and clinical samples from bone marrow, blood, lymph nodes and tonsils. A significant correlation was found between Southern blotting and Q-FISHFCM telomere length values (P = 0.002), The mean sub-telomeric DNA length of the tested cell lines and clinical samples was estimated to be 3.2 kbp, With the Q-FISHFCM method the fluorescence signal could be determined in different cell cycle phases, indicating that in human cells the vast majority of telomeric DNA is replicated early in S phase.

  • 13.
    Hultdin, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Grönlund, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Just, T
    Department of Immunocytochemistry, DAKO A/S, Glostrup, Denmark.
    Taneja, K
    Boston Probes Inc., Bedford, Massachusetts, USA.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Replication timing of human telomeric DNA and other repetitive sequences analyzed by fluorescence in situ hybridization and flow cytometry2001Inngår i: Experimental Cell Research, ISSN 0014-4827, Vol. 271, s. 223-229Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The replication timing of telomeres seems to differ between species. Yeast telomeres are late replicating, whereas limited data from very few human cell lines have indicated telomere replication throughout S phase. In the present study a series of permanent cell lines and patient samples was investigated using a flow cytometric approach for telomere length determination based on in situ hybridization using peptide nucleic acid probes and DNA staining. This method permits selective analysis of cells in specific phases of the cell cycle without perturbation of the cell cycle machinery. The timing of replication of telomeric C(3)TA(2) and T(2)AG(3) repeats was found to differ between individual samples and could precede or be concomitant with the replication of bulk DNA. Replication of the T(2)AG(3) strand seemed to occur somewhat later than that of the C(3)TA(2) strand in some samples. (GTG)(n) and other repetitive sequences generally showed a replication pattern similar to that of the bulk of DNA with slightly individual differences, whereas centromeric DNA repeats consistently replicated within a short time frame in late S phase. The apparent variability in replication timing seen for telomeric DNA might suggest individual differences in firing of replication origins.

  • 14.
    Hultdin, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rosenquist, R
    Thunberg, U
    Tobin, G
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Johnson, A
    Sundström, C
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Association between telomere length and V-H gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications2003Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 88, nr 4, s. 593-598Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The immunoglobulin V-H gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V-H genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated VH genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and VH gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between VH gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 63 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months), Furthermore, the I-g gene sequence data revealed that samples with high mutations frequency (> 6%) had long telomeres (similar to 8 kbp). Thus, both the telomere and VH gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction. (C) 2003 Cancer Research UK.

  • 15.
    Hultdin, Magnus
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Sundström, Gunnel
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Lundström, Berith
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Samuelsson, Jan
    Birgegård, Gunnar
    Engström Laurent, Anna
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Progression of bone marrow fibrosis in patients with essential thrombocythemia and polycythemia vera during anagrelide treatment.2007Inngår i: Med Oncol, ISSN 1357-0560, Vol. 24, nr 1, s. 63-70Artikkel i tidsskrift (Fagfellevurdert)
  • 16.
    Kolan, Shrikant S.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Lidström, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Björk, Karl
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Forsell, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Modulation of lymphoma growth by a selective serotonin receptor antagonist2017Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, nr 4, s. 343-343Artikkel i tidsskrift (Annet vitenskapelig)
  • 17.
    Kolan, Shrikant S
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Lidström, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Mediavilla, Tomás
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Dernstedt, Andy
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Björk, Karl
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Marcellino, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Forsell, Mattias N. E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Growth-inhibition of cell lines derived from B cell lymphomas through antagonism of serotonin receptor signaling2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 4276Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A majority of lymphomas are derived from B cells and novel treatments are required to treat refractory disease. Neurotransmitters such as serotonin and dopamine influence activation of B cells and the effects of a selective serotonin 1A receptor (5HT1A) antagonist on growth of a number of B cell-derived lymphoma cell lines were investigated. We confirmed the expression of 5HT1A in human lymphoma tissue and in several well-defined experimental cell lines. We discovered that the pharmacological inhibition of 5HT1A led to the reduced proliferation of B cell-derived lymphoma cell lines together with DNA damage, ROS-independent caspase activation and apoptosis in a large fraction of cells. Residual live cells were found ‘locked’ in a non-proliferative state in which a selective transcriptional and translational shutdown of genes important for cell proliferation and metabolism occurred (e.g., AKT, GSK-3β, cMYC and p53). Strikingly, inhibition of 5HT1A regulated mitochondrial activity through a rapid reduction of mitochondrial membrane potential and reducing dehydrogenase activity. Collectively, our data suggest 5HT1A antagonism as a novel adjuvant to established cancer treatment regimens to further inhibit lymphoma growth.

    Fulltekst (pdf)
    fulltext
  • 18. Mansouri, Larry
    et al.
    Noerenberg, Daniel
    Young, Emma
    Mylonas, Elena
    Abdulla, Maysaa
    Frick, Mareike
    Asmar, Fazila
    Ljungstroem, Viktor
    Schneider, Markus
    Yoshida, Kenichi
    Skaftason, Aron
    Pandzic, Tatjana
    Gonzalez, Blanca
    Tasidou, Anna
    Waldhueter, Nils
    Rivas-Delgado, Alfredo
    Angelopoulou, Maria
    Ziepert, Marita
    Arends, Christopher Maximilian
    Couronne, Lucile
    Lenze, Dido
    Baldus, Claudia D.
    Bastard, Christian
    Okosun, Jessica
    Fitzgibbon, Jude
    Doerken, Bernd
    Drexler, Hans G.
    Roos-Weil, Damien
    Schmitt, Clemens A.
    Munch-Petersen, Helga D.
    Zenz, Thorsten
    Hansmann, Martin-Leo
    Strefford, Jonathan C.
    Enblad, Gunilla
    Bernard, Olivier A.
    Ralfkiaer, Elisabeth
    Erlanson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Korkolopoulou, Penelope
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Papadaki, Theodora
    Gronbaek, Kirsten
    Lopez-Guillermo, Armando
    Ogawa, Seishi
    Kuppers, Ralf
    Stamatopoulos, Kostas
    Stavroyianni, Niki
    Kanellis, George
    Rosenwald, Andreas
    Campo, Elias
    Amini, Rose-Marie
    Ott, German
    Vassilakopoulos, Theodoros P.
    Hummel, Michael
    Rosenquist, Richard
    Damm, Frederik
    Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma2016Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 128, nr 23, s. 2666-2670Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We recently reported a truncating deletion in the NFKBIE gene, which encodes IkB epsilon, a negative feedback regulator of NF-kB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (< 2%), slightly higher frequencies were seen in diffuse large B- cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases [22.7%]) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases [27.3%]). NFKBIE-deleted PMBL patients were more often therapy refractory (P =.022) and displayed inferior outcome compared with wild- type patients (5-year survival, 59% vs 78%; P = .034); however, they appeared to benefit from radiotherapy P = .022) and rituximab-containing regimens (P = .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P =.003) and when restricting the analysis to immunochemotherapy-treated patients (P = .008). Whole-exome sequencing and gene expression profiling verified the importance of NF-kB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.

  • 19. Menter, Thomas
    et al.
    Tzankov, Alexandar
    Zucca, Emanuele
    Kimby, Eva
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Sundstrom, Christer
    Beiske, Klaus
    Cogliatti, Sergio
    Banz, Yara
    Cathomas, Gieri
    Katjalainen-Lindsberg, Marja-Liisa
    Grobholz, Rainer
    Mazzucchelli, Luca
    Sander, Birgitta
    Hawle, Hanne
    Hayoz, Stefanie
    Dirnhofer, Stefan
    Prognostic implications of the microenvironment for follicular lymphoma under immunomodulation therapy2020Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Follicular lymphoma (FL) constitutes a significant proportion of lymphomas and shows frequent relapses. Beyond conventional chemotherapy, new therapeutic approaches have emerged, focussing on the interplay between lymphoma cells and the microenvironment. Here we report the immunophenotypic investigation of the microenvironment of a clinically well-characterized prospective cohort (study SAKK35/10, NCT00544219) of 154 treatment-naive FL patients in need of therapy, who have been treated with rituximab only or a combination of rituximab and the immunomodulatory drug lenalidomide/Revlimid (R) A high ratio of CD4- to CD8-positive T cells (P = 0 center dot 009) and increased amounts of PD1(+) tumour-infiltrating T cells (P = 0 center dot 007) were associated with inferior progression-free survival in the whole cohort. Interestingly, the prognostic impact of PD1(+) T cells and the CD4/CD8 ratio lost its significance in the subgroup treated with R-2. In the latter group, high amounts of GATA3(+) T helper (Th2) equivalents were associated with better progression-free survival (P < 0 center dot 001). We identified tumour microenvironmental features that allow prognostic stratification with respect to immuno- and combined immuno- and immunomodulatory therapy. Our analysis indicates that lenalidomide may compensate the adverse prognostic implication of higher amounts of CD4(+) and, particularly, PD1(+) T cells and that it has favourable effects mainly in cases with higher amounts of Th2 equivalents.

  • 20.
    Norberg, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Rosén, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Raaschou-Jensen, Klas
    Kjeldsen, Lars
    Moilanen, Jukka S.
    Paulsson-Karisson, Ylva
    Baliakas, Panagiotis
    Lohi, Olli
    Ahmed, Aymen
    Kittang, Astrid O.
    Larsson, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Novel variants in Nordic patients referred for genetic testing of telomere-related disorders2018Inngår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 26, nr 6, s. 858-867Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Telomere-related disorders are a clinically and genetically heterogeneous group of disorders characterized by premature telomere shortening and proliferative failure of a variety of tissues. This study reports the spectrum of telomere-related gene variants and telomere length in Nordic patients referred for genetic testing due to suspected telomere-related disorder. We performed Sanger sequencing of the genes TERT, TERC, DKC1, and TINF2 on 135 unrelated index patients and measured telomere length by qPCR on DNA from peripheral blood leukocytes. We identified pathogenic or likely pathogenic variants in 10 index patients, all of which had short telomeres compared to age-matched healthy controls. Six of the 10 variants were novel; three in TERC (n.69_74dupAGGCGC, n.122_125delGCGG, and n.407_408delinsAA) and three in TERT (p.(D684G), p.(R774*), and p.(*1133Wext*39)). The high proportion of novel variants identified in our study highlights the need for solid interpretation of new variants that may be detected. Measurement of telomere length is a useful approach for evaluating pathogenicity of genetic variants associated with telomere-related disorders.

  • 21.
    Norrback, Karl-Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Dahlenborg, Katarina
    Osterman, Pia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Carlsson, Roland
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Telomerase regulation and telomere dynamics in germinal centers2001Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 67, nr 5-6, s. 309-317Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Telomere length maintenance, usually executed by telomerase, is a prerequisite for an extended or infinite division potential. Nevertheless most telomerase positive normal cells exhibit telomere shortening. This study details the telomerase expression and telomere dynamics in purified tonsil B cell subsets during the germinal center (GC) reaction. Significant telomere lengthening was observed as naive B cells matured to centroblasts and when centroblasts matured further to centrocytes, resulting in an increase in telomere length of about 4 kbp determined by Southern blotting. Immunopurified cell populations were also studied by fluorescence in situ hybridization and flow cytometry (flow-FISH) confirming that the GC B cells exhibited lengthened telomeres. These data were further verified in unpurified tonsil cells by combining flow-FISH and immunophenotyping using selected surface markers. Centroblasts expressed high levels of telomerase activity, which was increased in centrocytes, whereas resting naive, activated naive and memory B cells were telomerase activity negative. Expression levels of the catalytic subunit (hTERT) RNA paralleled the telomerase activity levels. The unique telomere elongation in GC B cells permits extensive proliferation during the GC reaction and provides the memory cells with a substantial increase in division potential. Understanding the telomere biology of GC cells is important in defining requirements for telomere elongation in vivo, with implications for the normal immune system as well as for lymphomas, and could provide insights into how the division potential of cells can be manipulated in vitro.

  • 22. Quist-Paulsen, P.
    et al.
    Toft, N.
    Heyman, M.
    Abrahamsson, J.
    Griskevicius, L.
    Hallbook, H.
    Jonsson, O. G.
    Palk, K.
    Vaitkeviciene, G.
    Vettenranta, K.
    Asberg, A.
    Frandsen, T. L.
    Opdahl, S.
    Marquart, H. V.
    Siitonen, S.
    Osnes, L. T.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Overgaard, U. M.
    Wartiovaara-Kautto, U.
    Schmiegelow, K.
    T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol2020Inngår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 34, nr 2, s. 347-357Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.

  • 23. Ranta, Susanna
    et al.
    Nilsson, Frans
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Harila-Saari, Arja
    Saft, Leonie
    Tani, Edneia
    Söderhall, Stefan
    Porwit, Anna
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Noren-Nyström, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Heyman, Mats
    Detection of Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia by Cytomorphology and Flow Cytometry of the Cerebrospinal Fluid2015Inngår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 62, nr 6, s. 951-956Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Therapy directed at the central nervous system (CNS) is an essential part of the treatment for childhood acute lymphoblastic leukemia (ALL). The current evaluation of CNS involvement based on cytomorphological examination of the cerebrospinal fluid (CSF) alone is not as sensitive with low cell counts as flow cytometric immunophenotyping (FCI) of the CSF. However, the importance of low CSF blasts counts at diagnosis is uncertain. We sought to determine the significance of FCI in relation to conventional morphological examination.

    Procedure: We retrospectively compared FCI of the CSF with cytomorphology at diagnosis or relapse of childhood ALL. All patients were diagnosed 2000–2012 in Stockholm or Umeå, Sweden. Clinical data were collected from medical records and the Nordic leukemia registry. Treatment assignment was based on morphological examination only.

    Results: The cohort was comprised of 214 patients with ALL. CSF involvement was detected by both methods in 20 patients, in 17 by FCI alone, and in one patient by cytomorphology alone. The relapse rate was higher for patients with negative cytology but positive FCI compared to those without CNS involvement using both methods. The difference was especially marked in the current protocol. However, none of the patients with negative CSF cytology but positive FCI had a CNS relapse.

    Conclusions: FCI of the CSF increased the detection rate of CNS involvement of ALL approximately two times compared to cytomorphology. Patients with low-level CNS involvement may benefit from additional intensified systemic or CNS-directed therapy, but larger studies are needed. 

  • 24.
    Sundström, Gunnel
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Dahl, Inger Marie S
    Hultdin, Magnus
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Lundström, Berit
    Umeå universitet, Medicinsk fakultet, Klinisk vetenskap, Öron- näs- och halssjukdomar.
    Wahlin, Anders
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Engström Laurent, Anna
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.2005Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 22, nr 1, s. 71-78Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The present study investigated potential age-related changes in human muscle spindles with respect to the intrafusal fiber-type content and myosin heavy chain (MyHC) composition in biceps brachii muscle. The total number of intrafusal fibers per spindle decreased significantly with aging, due to a significant reduction in the number of nuclear chain fibers. Nuclear chain fibers in old spindles were short and some showed novel expression of MyHC α-cardiac. The expression of MyHC α-cardiac in bag1 and bag2 fibers was greatly decreased in the A region. The expression of slow MyHC was increased in nuclear bag1 fibers and that of fetal MyHC decreased in bag2 fibers whereas the patterns of distribution of the remaing MyHC isoforms were generelly not affected by aging. We conclude that aging appears to have an important impact on muscle spindle composition. These changes in muscle spindle phenotype may reflect an age-related deterioration in sensory and motor innervation and are likely to have an impact in motor control in the elderly.

  • 25.
    Sundström, Gunnel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dahl, IMS
    Bone marrow hyaluronan and reticulin in patients with malignant disorders2010Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 27, nr 3, s. 618-623Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Myelofibrosis is commonly seen in patients with chronic myeloproliferative diseases and sometimes in myelodysplastic syndrome, acute leukaemia and lymphoproliferative diseases. The fibrotic process is evaluated by grading the amount of collagen deposited in the bone marrow interstitium. The established method to evaluate bone marrow fibrosis is staining for reticulin to visualise the collagen fibres. However, the extra cellular matrix does not only contain collagens but also other components, e.g. glycosaminoglycans of which hyaluronan is the most abundant. Hyaluronan is important for structural and cellular functions. Earlier studies have shown that there is a positive correlation between hyaluronan and reticulin staining in healthy volunteers and in patients with de novo acute myeloid leukaemia. In this study bone marrow biopsies from 43 patients with a malignant disease involving the bone marrow were compared with 18 patients with a malignant disease not involving the bone marrow. The intensity of hyaluronan grading was significantly higher in the patients with disease involving the bone marrow compared to the healthy controls but not compared to the patients without disease involving the bone marrow. The staining intensity of reticulin in the bone marrow was significantly higher in the patients with disease involving the bone marrow, compared to those without disease involving the bone marrow and to the controls. In all patients and the controls there was a correlation between hyaluronan and reticulin.

  • 26. Tobin, Gerard
    et al.
    Thunberg, Ulf
    Laurell, Anna
    Karlsson, Karin
    Aleskog, Anna
    Willander, Kerstin
    Söderberg, Ola
    Merup, Mats
    Vilpo, Juhani
    Hultdin, Magnus
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Sundström, Christer
    Roos, Göran
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Rosenquist, Richard
    Patients with chronic lymphocytic leukemia with mutated VH genes presenting with Binet stage B or C form a subgroup with a poor outcome.2005Inngår i: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Haematologica, Vol. 90, nr 4, s. 465-469Artikkel i tidsskrift (Fagfellevurdert)
1 - 26 of 26
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf