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.
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.
Whitehead
V M
VM
The Penny Cole Hematology Research Laboratory, McGill University, Montreal Children's Hospital Research Institute, Quebec.
Payment
C
C
Cooley
L
L
Lauer
S J
SJ
Mahoney
D H
DH
Shuster
J J
JJ
Vuchich
M J
MJ
Bernstein
M L
ML
Look
A T
AT
Pullen
D J
DJ
Camitta
B
B
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
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