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Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
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2004 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 104, no 8, 2452-2457 p.Article in journal (Refereed) PublishedText
Abstract [en]

The t(12;21) (p13;q22) translocation resulting in ETV6/RUNX1 (previously named TEL/AML1) gene fusion is present in about 25% of children with precursor B-lineage acute lymphoblastic leukemia (B-ALL). We successfully tested 275 precursor BALL samples from children aged 1 to 17 years to determine the relation between t(12;21) and in vitro cellular drug resistance, measured by the fluorometric microculture cytotoxicity assay (FMCA). Samples from 83 patients (30%) were positive for t(12;21). The ETV6/RUNX1(+) samples were significantly more sensitive than ETV6/RUNX1(-) samples to doxorubicin, etoposide, amsacrine, and dexamethasone, whereas the opposite was true for cytarabine. After matching for unevenly distributed patient characteristics, that is, excluding patients with high hyperdiploidy (> 51 chromosomes), t(g;22), t(1;19), or 11q23 rearrangement, the ETV6/RUNX1(+) samples remained significantly more sensitive to doxorubicin (P = .001) and etoposide (P = .001). For the other drugs tested (amsacrine, cytarabine, dexamethasone, prednisolone, vincristine, 6-thioguanine, and 4-hydroper-oxy-cyclophosphamide), no significant difference in cellular drug sensitivity was found. In conclusion, we found that the presence of the t(12;21) translocation in childhood precursor B-ALL is associated with a high tumor cell sensitivity to doxorubicin and etoposide. High throughput techniques should now be used to elucidate the cellular mechanisms by which ETV6/RUNX1 gene fusion is linked to increased sensitivity to these drugs.

Place, publisher, year, edition, pages
Washington: American society of hematology , 2004. Vol. 104, no 8, 2452-2457 p.
Keyword [en]
microculture cytotoxicity assay, TEL/AML1 fusion, tumor cells, clinical significance, gene fusion, ETV6 gene, children, resistance, series, abnormalities
National Category
Hematology
Identifiers
URN: urn:nbn:se:umu:diva-122147DOI: 10.1182/blood-2003-12-4426ISI: 000224378300042PubMedID: 15217836OAI: oai:DiVA.org:umu-122147DiVA: diva2:941516
Available from: 2016-06-22 Created: 2016-06-15 Last updated: 2016-06-22Bibliographically approved

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Forestier, Erik
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