title: Translocations involving chromosome 12p11-13, methotrexate metabolism, and outcome in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.
abstract: 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.
authors.affiliation: Penny Cole Hematology Research Laboratory, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
authors.forename: V M
authors.initials: VM
authors.lastname: Whitehead
authors.forename: M J
authors.initials: MJ
authors.lastname: Vuchich
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: C
authors.initials: C
authors.lastname: Payment
authors.forename: M L
authors.initials: ML
authors.lastname: Bernstein
authors.forename: J J
authors.initials: JJ
authors.lastname: Akabutu
authors.forename: T
authors.initials: T
authors.lastname: Bowen
authors.forename: B A
authors.initials: BA
authors.lastname: Kamen
authors.forename: M S
authors.initials: MS
authors.lastname: Watson
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: 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
chemical_list: 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