Medical College of Wisconsin
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The association of the TEL-AML1 chromosomal translocation with the accumulation of methotrexate polyglutamates in lymphoblasts and with ploidy in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Leukemia 2001 Jul;15(7):1081-8 PMID: 11455977

Pubmed ID

11455977

Abstract

Lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia (BpALL) with chromosomal hyperdiploidy and with translocations affecting chromosome 12p11-13, accumulate high and low levels of methotrexate polyglutamates (MTXPGs), respectively. Recently a cryptic translocation, t(12;21) (p13;q22), has been demonstrated by molecular and fluorescence in situ hybridization techniques in this disease. The chimeric TEL-AML1 transcript, which has been associated with this translocation, can be detected in up to 25% of children with BpALL. We detected the TEL-AML1 and/or the AML1-TEL transcript in 30 (33%) of 91 patients studied. Levels of lymphoblast MTXPGs were lower in those with than in those without the TEL-AML1 translocation (P = 0.004). Hyperdiploidy was rare in lymphoblasts with the TEL-AML1 translocation (P = 0.047). Both ploidy (P= 0.0015) and TEL-AML1 status (P= 0.0043) were independently and significantly correlated with the log of the lymphoblast MTXPG level. However, the presence of TEL-AML1 or of hyperdiploidy accounted for only 22% of the variation of this value. Our results imply that each of 1.16 > or = DI and the presence of the TEL-AML1 translocation confers a 50% decrease in lymphoblast MTXPG level. When planning reduction of therapy for either of the two excellent outcome categories of hyperdiploid or TEL-AML1 BpALL, one should consider the difference between these two subgroups in the ability of lymphoblasts to accumulate MTXPGs.

Author List

Whitehead VM, Payment C, Cooley L, Lauer SJ, Mahoney DH, Shuster JJ, Vuchich MJ, Bernstein ML, Look AT, Pullen DJ, Camitta B

Author

Bruce M. Camitta MD Clinical Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-0034906512   21 Citations

MESH terms used to index this publication - Major topics in bold

Child
Child, Preschool
Core Binding Factor Alpha 2 Subunit
Female
Humans
Infant
Lymphocytes
Male
Methotrexate
Oncogene Proteins, Fusion
Ploidies
Polyglutamic Acid
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Translocation, Genetic
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e