title: 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.
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.
authors.affiliation: The Penny Cole Hematology Research Laboratory, McGill University, Montreal Children's Hospital Research Institute, Quebec.
authors.forename: V M
authors.initials: VM
authors.lastname: Whitehead
authors.forename: C
authors.initials: C
authors.lastname: Payment
authors.forename: L
authors.initials: L
authors.lastname: Cooley
authors.forename: S J
authors.initials: SJ
authors.lastname: Lauer
authors.forename: D H
authors.initials: DH
authors.lastname: Mahoney
authors.forename: J J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: M J
authors.initials: MJ
authors.lastname: Vuchich
authors.forename: M L
authors.initials: ML
authors.lastname: Bernstein
authors.forename: A T
authors.initials: AT
authors.lastname: Look
authors.forename: D J
authors.initials: DJ
authors.lastname: Pullen
authors.forename: B
authors.initials: B
authors.lastname: Camitta
mesh_terms: D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000031:analogs & derivatives / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011003:Ploidies; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D008727:Methotrexate; D015514:Oncogene Proteins, Fusion; D011099:Polyglutamic Acid; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C014085:methotrexate polyglutamate