SEARCH:   Advanced

Blood, 15 October 2004, Vol. 104, No. 8, pp. 2452-2457. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2003-12-4426. This Article Full Text (PDF) All Versions of this Article: 2003-12-4426v1 104/8/2452    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Frost, B.-M. E Articles by Lonnerholm, G. Search for Related Content PubMed PubMed Citation Articles by Frost, B.-M. E Articles by Lonnerholm, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 5, 2004 Accepted March 18, 2004 Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia: On behalf of the Nordic Society for Paediatric Haematology and Oncology Britt-Marie E Frost*, Erik Forestier, Goran Gustafsson, Peter Nygren, Marit Hellebostad, Olafur G Jonsson, Jukka Kanerva, Kjeld Schmiegelow, Rolf Larsson, and Gudmar Lonnerholm Department of Womens and Childrens Health, University Childrens Hospital, Uppsala, Sweden Department of Clinical Sciences, University of Umea, Umea, Sweden Department of Pediatric Oncology, Karolinska Institute, Stockholm, Sweden Department of Oncology, Radiology and Clinical Immunology, University Hospital, Uppsala, Sweden Department of Pediatrics, Ulleval University Hospital, Oslo, Norway Department of Pediatrics, Landspitali University Hospital, Reykjavik, Iceland Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland Pediatric Clinic II, Rigshospitalet, Copenhagen, Denmark Department of Medical Sciences, Section of Pharmacology, University Hospital, Uppsala, Sweden * Corresponding author; email: britt-marie.frost{at}kbh.uu.se. 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 (ALL). We successfully tested 275 precursor B ALL samples from children aged 1-17 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-positive samples were significantly more sensitive than ETV6/RUNX1-negative samples to doxorubicin, etoposide, amsacrine, and dexamethasone, while the opposite was true for cytarabine. After matching for unevenly distributed patient characteristics, i.e. excluding patients with high hyperdiploidy (>51 chromosomes), t(9;22), t(1;19) and/or 11q23 rearrangement, the ETV6/RUNX1-positive samples remained significantly more sensitive to doxorubicin (p=0.001) and etoposide (p=0.001). For the other drugs tested (amsacrine, cytarabine, dexamethasone, prednisolone, vincristine, 6-thioguanine, and 4-hydroperoxy-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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Inthal, G. Krapf, D. Beck, R. Joas, M. O. Kauer, L. Orel, G. Fuka, G. Mann, and E. R. Panzer-Grumayer Role of the Erythropoietin Receptor in ETV6/RUNX1-Positive Acute Lymphoblastic Leukemia Clin. Cancer Res., November 15, 2008; 14(22): 7196 - 7204. [Abstract] [Full Text] [PDF] B. Accordi, S. Pillozzi, M. C. Dell'Orto, G. Cazzaniga, A. Arcangeli, G. t. Kronnie, and G. Basso Hepatocyte Growth Factor Receptor c-MET Is Associated with FAS and When Activated Enhances Drug-induced Apoptosis in Pediatric B Acute Lymphoblastic Leukemia with TEL-AML1 Translocation J. Biol. Chem., October 5, 2007; 282(40): 29384 - 29393. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020