Accumulation of methotrexate polyglutamates, ploidy and trisomies of both chromosomes 4 and 10 in lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Leuk Lymphoma 1998 Nov;31(5-6):507-19
Date
01/28/1999Pubmed ID
9922041DOI
10.3109/10428199809057610Scopus ID
2-s2.0-0032449896 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
Levels of accumulation of methotrexate polyglutamates were measured in vitro in lymphoblasts obtained at diagnosis from children with B-progenitor cell acute lymphoblastic leukemia (pro-B ALL). They were compared to numerical and structural chromosomal abnormalities present in these leukemic cells. In a series of 95 patients, the percent with high lymphoblast methotrexate polyglutamate levels increased with the increase in modal number of total chromosomes (p<0.001). Thus, lymphoblast methotrexate polyglutamate accumulation appeared to be closely linked to the extent of hyperdiploidy in childhood pro-B ALL. Lymphoblasts from 35 (88%) of the 40 children with hyperdiploid (>50 chromosomes) and 23 (88%) of 26 with hyperdiploid (DNA Index >1.16) pro-B ALL accumulated high levels of methotrexate polyglutamate, suggesting that they were more sensitive to methotrexate cytotoxicity. While children with hyperdiploid (DNA Index >1.16) pro-B ALL have a good prognosis, those with trisomies of both chromosomes 4 and 10, almost all of whom are hyperdiploid, have an even better outcome. There was no significant difference in methotrexate polyglutamate levels in lymphoblasts from 19 children with and 21 without trisomies of both chromosomes 4 and 10 (p = 0.25). The improved response to multi-agent chemotherapy conferred by the presence of trisomies of both chromosomes 4 and 10 in such patients may be due to increased sensitivity of their lymphoblasts to one or more anti-leukemic agents in addition to methotrexate.
Author List
Whitehead VM, Vuchich MJ, Cooley LD, Lauer SJ, Mahoney DH, Shuster JJ, Payment C, Koch PA, Akabutu JJ, Bowen T, Kamen BA, Ravindranath Y, Emami A, Look AT, Beardsley GP, Pullen DJ, Camitta BMESH terms used to index this publication - Major topics in bold
AdolescentAneuploidy
Antineoplastic Combined Chemotherapy Protocols
Bone Marrow
Child
Child, Preschool
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 4
Female
Folic Acid
Humans
Male
Methotrexate
Neoplastic Stem Cells
Peptide Synthases
Polyglutamic Acid
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Trisomy