Translocations involving chromosome 12p11-13, methotrexate metabolism, and outcome in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.
Children with B-progenitor cell acute lymphoblastic leukemia whose lymphoblasts at diagnosis accumulate high levels of methotrexate (MTX) and MTX polyglutamates (MTXPGs) appear to have a good prognosis. This has been attributed to increased sensitivity of their blast cells to MTX. However, the proportion of children who are cured of B-progenitor cell acute lymphoblastic leukemia exceeds the number whose lymphoblasts accumulate high MTXPG levels. We report that lymphoblasts from patients with < 50 chromosomes who have translocations that involve the short arm of chromosome 12 accumulate low levels of MTXPGs. These patients appear to have an excellent survival because none of 14 patients with translocations affecting 12p has relapsed, 26-79 months following diagnosis.
Whitehead
V M
VM
Penny Cole Hematology Research Laboratory, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
Vuchich
M J
MJ
Cooley
L
L
Lauer
S J
SJ
Mahoney
D H
DH
Shuster
J J
JJ
Payment
C
C
Bernstein
M L
ML
Akabutu
J J
JJ
Bowen
T
T
Kamen
B A
BA
Watson
M S
MS
Look
A T
AT
Pullen
D J
DJ
Camitta
B
B
D000964:Antimetabolites, Antineoplastic / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000378:metabolism*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D008727:Methotrexate; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein