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 OncologyGroup study

Lymphoblasts from children with B-progenitor cell acute lymphoblastic leuke mia (BpALL) with chromosomal hyperdiploidy and with translocations affectin g chromosome 12p11-13, accumulate high and low levels of methotrexate polyg lutamates (MTXPGs), respectively. Recently a cryptic translocation, t(12;21 ) (p13;q22), has been demonstrated by molecular and fluorescence in situ hy bridization techniques in this disease. The chimeric TEL-AML1 transcript, w hich 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 tr anscript in 30 (33%) of 91 patients studied. Levels of lymphoblast MTXPGs w ere lower in those with than in those without the TEL-AML1 translocation (P = 0.004). Hyperdiploidy was rare in lymphoblasts with the TEL-AML1 translo cation (P = 0.047). Both ploidy (P = 0.0015) and TEL-AML1 status (P = 0.004 3) were independently and significantly correlated with the log of the lymp hoblast MTXPG level. However, the presence of TEL-AML1 or of hyperdiploidy accounted for only 22% of the variation of this value. Our results imply th at each of 1.16 greater than or equal to DI and the presence of the TEL-AML 1 translocation confers a 50% decrease in lymphoblast MTXPG level. When pla nning reduction of therapy for either of the two excellent outcome categori es of hyperdiploid or TEL-AML1 BpALL, one should consider the difference be tween these two subgroups in the ability of lymphoblasts to accumulate MTXP Gs.