umu.sePublications
Change search
Refine search result
1 - 27 of 27
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Davidsson, J
    et al.
    Paulsson, K
    Lindgren, D
    Lilljebjörn, H
    Chaplin, T
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Andersen, M K
    Nordgren, A
    Rosenquist, R
    Fioretos, T
    Young, B D
    Johansson, B
    Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations.2010In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 24, no 5, p. 924-31Article in journal (Refereed)
    Abstract [en]

    Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution patterns. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (P<0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. On the basis of the genetic relationship between the paired samples, three groups were delineated: (1) identical genetic changes at diagnosis and relapse (2 of 11 cases), (2) clonal evolution with all changes at diagnosis being present at relapse (2 of 11) and (3) clonal evolution with some changes conserved, lost or gained (7 of 11), suggesting the presence of a preleukemic clone. This ancestral clone was characterized by numerical changes only, with structural changes and RTK-RAS mutations being secondary to the high hyperdiploid pattern.

  • 2. Frost, B M
    et al.
    Forestier, E
    Gustafsson, G
    Nygren, P
    Hellebostad, M
    Jonmundsson, G
    Kanerva, J
    Schmiegelow, K
    Larsson, R
    Lönnerholm, G
    Translocation t(1;19) is related to low cellular drug resistance in childhood acute lymphoblastic leukaemia.2005In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 19, no 1, p. 165-9Article in journal (Refereed)
  • 3.
    Gunnarsson, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hoglund, M.
    Stenke, L.
    Sandin, F.
    Bjorkholm, M.
    Dreimane, A.
    Lambe, M.
    Markevarn, B.
    Olsson-Stromberg, U.
    Wadenvik, H.
    Richter, J.
    Sjalander, A.
    No increased prevalence of malignancies among first-degree relatives of 800 patients with chronic myeloid leukemia: a population-based study in Sweden2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 8, p. 1825-1827Article in journal (Refereed)
  • 4.
    Gunnarsson, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Höglund, M.
    Stenke, L.
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Sandin, F.
    Björkholm, M.
    Dreimane, A.
    Lambe, M.
    Markevärn, Berit
    Olsson-Strömberg, U.
    Wadenvik, H.
    Richter, J.
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia2016In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, no 7, p. 1562-1567Article in journal (Refereed)
    Abstract [en]

    We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.

  • 5. Harrison, C. J.
    et al.
    Moorman, A. V.
    Schwab, C.
    Carroll, A. J.
    Raetz, E. A.
    Devidas, M.
    Strehl, S.
    Nebral, K.
    Harbott, J.
    Teigler-Schlegel, A.
    Zimmerman, M.
    Dastuge, N.
    Baruchel, A.
    Soulier, J.
    Auclerc, M-F
    Attarbaschi, A.
    Mann, G.
    Stark, B.
    Cazzaniga, G.
    Chilton, L.
    Vandenberghe, P.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Haltrich, I.
    Raimondi, S. C.
    Parihar, M.
    Bourquin, J-P
    Tchinda, J.
    Haferlach, C.
    Vora, A.
    Hunger, S. P.
    Heerema, N. A.
    Haas, O. A.
    An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome2014In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 28, no 5, p. 1015-1021Article in journal (Refereed)
    Abstract [en]

    Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.

  • 6.
    Hedenus, Michael
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Birgegård, Gunnar
    Näsman, Per
    Ahlberg, Lucia
    Karlsson, Torbjörn
    Lauri, Birgitta
    Lundin, Jeanette
    Lärfars, Gerd
    Österborg, Anders
    Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study.2007In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 21, no 4, p. 627-632Article in journal (Refereed)
  • 7. Hirvonen, Elina A. M.
    et al.
    Peuhkuri, Saara
    Norberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Hannula-Jouppi, Katariina
    Välimaa, Hannamari
    Kilpivaara, Outi
    Wartiovaara-Kautto, Ulla
    Characterization of an X-chromosome-linked telomere biology disorder in females with DKC1 mutation2019In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 33, no 1, p. 275-278Article in journal (Refereed)
  • 8. Ilander, M
    et al.
    Olsson-Strömberg, U
    Schlums, H
    Guilhot, J
    Brück, O
    Lähteenmäki, H
    Kasanen, T
    Koskenvesa, P
    Söderlund, S
    Höglund, M
    Markevärn, B
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lotfi, K
    Dreimane, A
    Lübking, A
    Holm, E
    Björeman, M
    Lehmann, S
    Stenke, L
    Ohm, L
    Gedde-Dahl, T
    Majeed, W
    Ehrencrona, H
    Koskela, S
    Saussele, S
    Mahon, F-X
    Porkka, K
    Hjorth-Hansen, H
    Bryceson, Y T
    Richter, J
    Mustjoki, S
    Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 5, p. 1108-1116Article in journal (Refereed)
    Abstract [en]

    Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56(bright) NK cells had decreased relapse free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.

  • 9. Juliusson, G.
    et al.
    Abrahamsson, J.
    Lazarevic, V.
    Antunovic, P.
    Derolf, A.
    Garelius, H.
    Lehmann, S.
    Myhr-Eriksson, K.
    Mollgard, L.
    Uggla, B.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wennstrom, L.
    Hoglund, M.
    Prevalence and characteristics of survivors from acute myeloid leukemia in Sweden2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 3, p. 728-731Article in journal (Refereed)
  • 10. Junlen, H. R.
    et al.
    Peterson, S.
    Kimby, E.
    Lockmer, S.
    Linden, O.
    Nilsson-Ehle, H.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hagberg, H.
    Radlund, A.
    Hagberg, O.
    Wahlin, B. E.
    Follicular lymphoma in Sweden: nationwide improved survival in the rituximab era, particularly in elderly women: a Swedish Lymphoma Registry Study2015In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 29, no 3, p. 668-676Article in journal (Refereed)
    Abstract [en]

    Treatment for follicular lymphoma (FL) improved with rituximab. In Sweden, first-line rituximab was gradually introduced between 2003 and 2007, with regional differences. The first national guidelines for FL were published in November 2007, recommending rituximab in first-line therapy. Using the population-based Swedish Lymphoma Registry, 2641 patients diagnosed with FL from 2000 to 2010 were identified and characterized by year and region of diagnosis, age (median, 65 years), gender (50% men), first-line therapy and clinical risk factors. Overall and relative survivals were estimated by calendar periods (2000-2002, 2003-2007 and 2008-2010) and region of diagnosis. With each period, first-line rituximab use and survival increased. Survival was superior in regions where rituximab was quickly adopted and inferior where slowly adopted. These differences were independent in multivariable analyses. Ten-year relative survival for patients diagnosed 2003-2010 was 92%, 83%, 78% and 64% in the age groups 18-49, 50-59, 60-69 and. 70, respectively. With increasing rituximab use, male sex emerged as an adverse factor. Survival improved in all patient categories, particularly in elderly women. The introduction and the establishment of rituximab have led to a nationwide improvement in FL survival. However, rituximab might be inadequately dosed in younger women and men of all ages.

  • 11. Kaderi, M A
    et al.
    Norberg, M
    Murray, F
    Merup, M
    Sundström, C
    Roos, Göran
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Aleskog, A
    Karlsson, K
    Axelsson, T
    Tobin, G
    Rosenquist, R
    The BCL-2 promoter (-938C>A) polymorphism does not predict clinical outcome in chronic lymphocytic leukemia.2008In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 22, no 2, p. 339-343Article in journal (Other academic)
  • 12. Lehmann, Sören
    et al.
    Ravn, S
    Carlsson, L
    Antunovic, P
    Deneberg, S
    Möllgård, L
    Rangert Derolf, Å
    Stockelberg, D
    Tidefelt, U
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wennström, L
    Högberg, M
    Juliusson, G
    Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry2011In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, no 7, p. 1128-1134Article in journal (Refereed)
    Abstract [en]

    Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100 000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients <40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

  • 13. Modvig, S.
    et al.
    Madsen, H. O.
    Siitonen, S. M.
    Rosthoj, S.
    Tierens, A.
    Juvonen, V
    Osnes, L. T. N.
    Valerhaugen, H.
    Hultdin, M.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thorn, I
    Matuzeviciene, R.
    Stoskus, M.
    Marincevic, M.
    Fogelstrand, L.
    Lilleorg, A.
    Toft, N.
    Jonsson, O. G.
    Pruunsild, K.
    Vaitkeviciene, G.
    Vettenranta, K.
    Lund, B.
    Abrahamsson, J.
    Schmiegelow, K.
    Marquart, H. , V
    Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia2019In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 33, no 6, p. 1324-1336Article in journal (Refereed)
    Abstract [en]

    Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10−3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4–9.0, p = 0.008) for day 29 FCM-MRD ≥ 10−3and 5.6 (95% CI 2.0–16, p = 0.001) for PCR-MRD ≥ 10−3 compared with MRD < 10−3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10−4–<10−3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10−4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10−4 had a cumulative incidence of relapse of 2.3% (95% CI 0–6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.

  • 14. Moorman, AV
    et al.
    Raimondi, SC
    Pui, CH
    Baruchel, A
    Biondi, A
    Carroll, AJ
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Gaynon, PS
    Harbott, J
    Harms, DO
    Heerema, N
    Pieters, R
    Schrappe, M
    Silverman, LB
    Vilmer, E
    Harrison, CJ
    No prognostic effect of additional chromosomal abnormalities in children with acute lymphoblastic leukemia and 11q23 abnormalities2005In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 19, no 4, p. 557-563Article in journal (Refereed)
    Abstract [en]

    This study characterized the additional chromosomal abnormalities (ACA) associated with 11q23 rearrangements in 450 infants and children with acute lymphoblastic leukemia ( ALL) and examined the impact of these ACA on survival. Overall, 213 (47%) cases had ACA but the incidence varied according to patient age and 11q23 subgroup. Infants and patients with t(4; 11)(q21; q23) had the lowest incidence of ACA (50/182 (27%) and 57/216 (26%) respectively), whereas patients with del( 11)( q23) had the highest incidence (66/93 (71%)). Del( 11)( q23) abnormalities were heterogeneous and occasionally secondary to t( 9; 22)(q34; q11.2). Thus, patients with del( 11)( q23) comprised a separate biological entity, which was clearly distinct from those with an 11q23 translocation. The most frequent specific ACA were trisomy X ( n = 38), abnormal 12p ( n = 32), abnormal 9p ( n = 28) and del( 6q) ( n = 19). The presence of ACA did not change the 5 year event-free survival estimates among children (56% (95% CI 46 - 65%) vs 62% (54 - 69%)) or infants (22% ( 15 - 29%) vs 18% ( 9 - 29%)), nor when the different 11q23 subgroups were analyzed separately. This study has conclusively demonstrated that there is no prognostic effect of secondary chromosomal changes in association with 11q23 abnormalities in childhood ALL. However, characterization of these ACA is important to determine their potential role in initiation of MLL driven leukemogenesis.

  • 15. Mustjoki, S
    et al.
    Richter, J
    Barbany, G
    Ehrencrona, H
    Fioretos, T
    Gedde-Dahl, T
    Gjertsen, BT
    Hovland, R
    Hernesniemi, S
    Josefsen, D
    Koskenvesa, P
    Dybedal, I
    Markevärn, Berit
    Umeå University, Faculty of Medicine.
    Olofsson, T.
    Olsson-Stromberg, U.
    Rapakko, K.
    Thunberg, S.
    Stenke, L.
    Simonsson, B.
    Porkka, K.
    Hjorth-Hansen, H.
    Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients2013In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 27, no 7, p. 1520-1526Article in journal (Refereed)
    Abstract [en]

    Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38=) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the diagnosis and during imatinib or dasatinib therapy (ClinicalTrials.gov NCT00852566). At diagnosis, the proportion of LSCs varied markedly (1-100%) between individual patients with a significantly lower median value as compared with LPCs (79% vs 96%, respectively, P = 0.0001). The LSC burden correlated with leukocyte count, spleen size, hemoglobin and blast percentage. A low initial LSC percentage was associated with less therapy-related hematological toxicity and superior cytogenetic and molecular responses. After initiation of TKI therapy, the LPCs and LSCs rapidly decreased in both therapy groups, but at 3 months time point the median LPC level was significantly lower in dasatinib group compared with imatinib patients (0.05% vs 0.68%, P = 0.032). These data detail for the first time the prognostic significance of the LSC burden at diagnosis and show that in contrast to in vitro data, TKI therapy rapidly eradicates the majority of LSCs in patients.

  • 16. Nordlund, J.
    et al.
    Kiialainen, A.
    Karlberg, O.
    Berglund, E. C.
    Goransson-Kultima, H.
    Sonderkaer, M.
    Nielsen, K. L.
    Gustafsson, M. G.
    Behrendtz, M.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Perkkio, M.
    Soderhall, S.
    Lonnerholm, G.
    Syvanen, A-C
    Digital gene expression profiling of primary acute lymphoblastic leukemia cells2012In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 26, no 6, p. 1218-1227Article in journal (Refereed)
    Abstract [en]

    We determined the genome-wide digital gene expression (DGE) profiles of primary acute lymphoblastic leukemia (ALL) cells from 21 patients taking advantage of `second-generation' sequencing technology. Patients included in this study represent four cytogenetically distinct subtypes of B-cell precursor (BCP) ALL and T-cell lineage ALL (T-ALL). The robustness of DGE combined with supervised classification by nearest shrunken centroids (NSC) was validated experimentally and by comparison with published expression data for large sets of ALL samples. Genes that were differentially expressed between BCP ALL subtypes were enriched to distinct signaling pathways with dic(9;20) enriched to TP53 signaling, t(9;22) to interferon signaling, as well as high hyperdiploidy and t(12;21) to apoptosis signaling. We also observed antisense tags expressed from the non-coding strand of similar to 50% of annotated genes, many of which were expressed in a subtype-specific pattern. Antisense tags from 17 gene regions unambiguously discriminated between the BCP ALL and T-ALL subtypes, and antisense tags from 76 gene regions discriminated between the 4 BCP subtypes. We observed a significant overlap of gene regions with alternative polyadenylation and antisense transcription (P<1 x 10(-15)). Our study using DGE profiling provided new insights into the RNA expression patterns in ALL cells.

  • 17.
    Norén-Nyström, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Botling, J
    Lönnerholm, G
    Porwit, A
    Heyman, M
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Bone marrow fibrosis in childhood acute lymphoblastic leukemia correlates to biological factors, treatment response and outcome2008In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 22, no 3, p. 504-510Article in journal (Refereed)
    Abstract [en]

    We retrospectively evaluated reticulin fiber density (RFD) in 166 diagnostic bone marrow (BM) biopsies and 62 biopsies obtained at treatment day 29 from children with acute lymphoblastic leukemia (ALL). Patients with B-cell precursor (BCP)-ALL showed higher RFD as compared to patients with T-cell ALL (P<0.001). RFD correlated negatively with white blood cell count (P=0.008) in BCP-ALL patients. Patients with high-hyperdiploid ALL (51–61 chromosomes), no high-risk criteria and low RFD showed a favorable outcome when compared to similar patients with high RFD (P=0.002). In BCP-ALL patients, RFD at diagnosis correlated to the levels of minimal residual disease (MRD) analyzed by flow cytometry on treatment day 29 (P=0.001). Accordingly, patients with MRD10-4 presented higher RFD at diagnosis compared to patients with MRD<10-4 (P=0.003). BCP-ALL patients with low RFD at diagnosis and a rapid reduction of RFD on day 29 had a favorable outcome compared to patients with the same baseline RFD level at diagnosis but a slow RFD reduction (P=0.041). To our knowledge, these findings are novel and may indicate BM fibrosis as a new valuable prognostic marker in childhood ALL. Expanded use of BM biopsy both at diagnosis and during follow-up is suggested.

  • 18.
    Norén-Nyström, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology. Patologi.
    Roos, Göran
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology. Patologi.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology. Patologi.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Clinical Sciences, Paediatrics. Pediatrik.
    Prognostic impact of vascular density and fibrosis in the bone marrow of children with high-risk acute lymphoblastic leukemia.2005In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 19, no 11, p. 1998-2001Article in journal (Other academic)
  • 19. Olsson, L
    et al.
    Castor, A
    Behrendtz, M
    Biloglav, A
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Paulsson, K
    Johansson, B
    Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 20112014In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 28, no 2, p. 302-310Article in journal (Refereed)
    Abstract [en]

    Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. As this occurs not only in the high risk but also in the standard/intermediate groups, the presently used risk stratification is suboptimal. The underlying mechanisms for treatment failure include the presence of genetic changes causing insensitivity to the therapy administered. To identify relapse-associated aberrations, we performed single-nucleotide polymorphism array analyses of 307 uniformly treated, consecutive pediatric ALL cases accrued during 1992-2011. Recurrent aberrations of 14 genes in patients who subsequently relapsed or had induction failure were detected. Of these, deletions/uniparental isodisomies of ADD3, ATP10A, EBF1, IKZF1, PAN3, RAG1, SPRED1 and TBL1XR1 were significantly more common in B-cell precursor ALL patients who relapsed compared with those remaining in complete remission. In univariate analyses, age (>= 10 years), white blood cell counts (>100 x 10(9)/l), t(9; 22)(q34; q11), MLL rearrangements, near-haploidy and deletions of ATP10A, IKZF1, SPRED1 and the pseudoautosomal 1 regions on Xp/Yp were significantly associated with decreased 10-year event-free survival, with IKZF1 abnormalities being an independent risk factor in multivariate analysis irrespective of the risk group. Older age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival. Thus, analyses of these genes provide clinically important information.

  • 20. Safavi, S.
    et al.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Barbany, G.
    Nord, K. H.
    Moorman, A. V.
    Harrison, C. J.
    Johansson, B.
    Paulsson, K.
    Loss of chromosomes is the primary event in near-haploid and low-hypodiploid acute lymphoblastic leukemia2013In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 27, no 1, p. 248-250Article in journal (Refereed)
  • 21. Schmiegelow, K
    et al.
    Forestier, E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hellebostad, M
    Heyman, M
    Kristinsson, J
    Söderhäll, S
    Taskinen, M
    Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia.2010In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 24, no 2, p. 345-54Article in journal (Refereed)
    Abstract [en]

    Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors. Improvements in systemic and intrathecal chemotherapy have reduced the use of central nervous system (CNS) irradiation to <10% of the patients and provided a 5-year risk of isolated CNS relapse of 2.6%. Improved risk stratification and chemotherapy have eliminated the previous independent prognostic significance of gender, CNS leukemia and translocation t(1;19)(q23;p13), whereas the post-induction level of minimal residual disease (MRD) has emerged as a new risk grouping feature. Infant leukemia, high leukocyte count, T-lineage immunophenotype, translocation t(4;11)(q21;q23) and hypodiploidy persist to be associated with lower cure rates. To reduce the overall toxicity of the treatment, including the risk of therapy-related second malignant neoplasms, the current NOPHO ALL-2008 protocol does not include CNS irradiation in first remission, the dose of 6-mercaptopurine is reduced for patients with low thiopurine methyltransferase activity, and the protocol restricts the use of hematopoietic stem cell transplantation in first remission to patients without morphological remission after induction therapy or with high levels of MRD after 3 months of therapy.

  • 22. Schmiegelow, K
    et al.
    Forestier, E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kristinsson, J
    Söderhäll, S
    Vettenranta, K
    Weinshilboum, R
    Wesenberg, F
    Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study2009In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 23, no 3, p. 557-564Article in journal (Refereed)
    Abstract [en]

    Myelotoxicity during thiopurine therapy is enhanced in patients, who because of single nucleotide polymorphisms have decreased activity of the enzyme thiopurine methyltransferase (TPMT) and thus more thiopurine converted into 6-thioguanine nucleotides. Of 601 children with acute lymphoblastic leukemia (ALL) who were treated by the NOPHO ALL-92 protocol, 117 had TPMT genotype determined, whereas for 484 patients only erythrocyte TPMT activity was available. The latter were classified as heterozygous, if TPMT activity was <14 IU/ml, or deficient (<1.0 IU/ml). 526 patients had TPMT wild type, 73 were presumed heterozygous, and two were TPMT deficient. Risk of relapse was higher for the 526 TPMT wild type patients than for the remaining 75 patients (18 vs 7%, P=0.03). In cox multivariate regression analysis, sex (male worse; P=0.06), age (higher age worse, P=0.02), and TPMT activity (wild type worse; P=0.02) were related to risk of relapse. Despite a lower probability of relapse, patients in the low TPMT activity group did not have superior survival (P=0.82), possibly because of an excess of secondary cancers among these 75 patients (P=0.07). These data suggest that children with ALL and TPMT wild type might have their cure rate improved, if the pharmacokinetics/-dynamics of TPMT low-activity patients could be mimicked without a concurrent excessive risk of second cancers.

  • 23. Schmiegelow, K
    et al.
    Heyman, M
    Gustafsson, G
    Lausen, B
    Wesenberg, F
    Kristinsson, J
    Vettenranta, K
    Schroeder, H
    Forestier, E
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rosthoej, S
    The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse.2010In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 24, no 4, p. 715-20Article in journal (Refereed)
    Abstract [en]

    Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (>or=10 years) and 176 non-adolescents (<10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) <50 x 10(9)/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS(12y):0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r(S)=0.36, P=0.02), which became nonsignificant for those who relapsed (r(S)=0.05, P=0.9). The best-fit multivariate Cox regression model to predict risk of relapse included mWBC and thiopurine methyltransferase activity, which methylates mercaptopurine and reduces the intracellular availability of cytotoxic 6-thioguanine nucleotides (coefficient: 0.11, P=0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient=0.65, P=0.003) than for non-adolescents (coefficient=0.42, P=0.04). Adolescents had higher mean neutrophil counts (P=0.002) than non-adolescents, but received nonsignificantly lower mercaptopurine and MTX doses during maintenance therapy. Red blood cell MTX levels were significantly related to the dose of MTX among adolescents who stayed in remission (r(S)=0.38, P=0.02), which was not the case for those who developed a relapse (r(S)=0.15, P=0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.

  • 24. Thomsen, Hauke
    et al.
    Chattopadhyay, Subhayan
    Weinhold, Niels
    Vodicka, Pavel
    Vodickova, Ludmila
    Hoffmann, Per
    Nöthen, Markus M
    Jöckel, Karl-Heinz
    Langer, Christian
    Hajek, Roman
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Ohlsson, Claes
    Späth, Florentin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Houlston, Richard
    Goldschmidt, Hartmut
    Hemminki, Kari
    Försti, Asta
    Genome-wide association study of monoclonal gammopathy of unknown significance (MGUS): comparison with multiple myeloma2019In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 33, no 7, p. 1817-1821Article in journal (Refereed)
  • 25. Toft, N.
    et al.
    Birgens, H.
    Abrahamsson, J.
    Griskevicius, L.
    Hallböök, H.
    Heyman, M.
    Klausen, T. W.
    Jónsson, O. G.
    Palk, K.
    Pruunsild, K.
    Quist-Paulsen, P.
    Vaitkeviciene, G.
    Vettenranta, K.
    Åsberg, A.
    Frandsen, T. L.
    Marquart, H. V.
    Madsen, H. O.
    Norén-Nyström, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schmiegelow, K.
    Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia2018In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, no 3, p. 606-615Article in journal (Refereed)
    Abstract [en]

    Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P = 0.53). Event-free survival rates (pEFS(5y)) were 89 +/- 1% (A), 80 +/- 3% (B) and 74 +/- 4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.

  • 26.
    Zachariadis, V
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Gauffin, F
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Kuchinskaya, E
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Heyman, M
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Schoumans, J
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Blennow, E
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Gustafsson, B
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Barbany, G
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Ehrencrona, H
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Cavelier, L
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Palmqvist, L
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lönnerholm, G
    Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden.
    Nordenskjöld, M
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Johansson, B
    Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nordgren, A
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial2011In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, no 4, p. 622-628Article in journal (Refereed)
    Abstract [en]

    The dic(9;20)(p13.2;q11.2) is reported to be present in ∼2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analyses-in a three-step manner-using probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P=0.002) and high hyperdiploidy (0.82; P=0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.

  • 27. Zachariadis, V.
    et al.
    Schoumans, J.
    Ofverholm, I.
    Barbany, G.
    Halvardsson, E.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, B.
    Nordenskjold, M.
    Nordgren, A.
    Detecting dic(9;20)(p13.2;p11.2)-positive B-cell precursor acute lymphoblastic leukemia in a clinical setting using fluorescence in situ hybridization2014In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 28, no 1, p. 196-198Article in journal (Refereed)
1 - 27 of 27
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf