Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia

2.50
Hdl Handle:
http://hdl.handle.net/2336/52433
Title:
Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia
Authors:
Frost, Britt-Marie; Forestier, Erik; Gustafsson, Göran; Nygren, Peter; Hellebostad, Marit; Jonsson, Olafur G; Kanerva, Jukka; Schmiegelow, Kjeld; Larsson, Rolf; Lönnerholm, Gudmar
Citation:
Blood. 2004, 104(8):2452-7
Issue Date:
15-Oct-2004
Abstract:
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 B-ALL 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(9; 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-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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/bloodjournal;104/8/2452

Full metadata record

DC FieldValue Language
dc.contributor.authorFrost, Britt-Marie-
dc.contributor.authorForestier, Erik-
dc.contributor.authorGustafsson, Göran-
dc.contributor.authorNygren, Peter-
dc.contributor.authorHellebostad, Marit-
dc.contributor.authorJonsson, Olafur G-
dc.contributor.authorKanerva, Jukka-
dc.contributor.authorSchmiegelow, Kjeld-
dc.contributor.authorLarsson, Rolf-
dc.contributor.authorLönnerholm, Gudmar-
dc.date.accessioned2009-03-05T16:40:37Z-
dc.date.available2009-03-05T16:40:37Z-
dc.date.issued2004-10-15-
dc.date.submitted2009-03-05-
dc.identifier.citationBlood. 2004, 104(8):2452-7en
dc.identifier.issn0006-4971-
dc.identifier.pmid15217836-
dc.identifier.doi10.1182/blood-2003-12-4426-
dc.identifier.urihttp://hdl.handle.net/2336/52433-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractThe 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 B-ALL 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(9; 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-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.en
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.relation.urlhttp://bloodjournal.hematologylibrary.org/cgi/content/abstract/bloodjournal;104/8/2452en
dc.subject.meshAdolescenten
dc.subject.meshCell Line, Tumoren
dc.subject.meshChilden
dc.subject.meshChild, Preschoolen
dc.subject.meshChromosomes, Human, Pair 12en
dc.subject.meshChromosomes, Human, Pair 21en
dc.subject.meshCore Binding Factor Alpha 2 Subuniten
dc.subject.meshDNA-Binding Proteinsen
dc.subject.meshDiploidyen
dc.subject.meshDoxorubicinen
dc.subject.meshDrug Resistance, Neoplasmen
dc.subject.meshEtoposideen
dc.subject.meshFemaleen
dc.subject.meshGene Orderen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshMaleen
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphomaen
dc.subject.meshProto-Oncogene Proteinsen
dc.subject.meshProto-Oncogene Proteins c-etsen
dc.subject.meshRepressor Proteinsen
dc.subject.meshTranscription Factorsen
dc.subject.meshTranslocation, Geneticen
dc.titleTranslocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemiaen
dc.typeArticleen
dc.contributor.departmentDepartment of Women's and Children's Health, University Children's Hospital, SE-751 85 Uppsala, Sweden. britt-marie.frost@kbh.uu.seen
dc.identifier.journalBlooden

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