Accumulation of High Levels of Methotrexate Polyglutamates in Lymphoblasts From Children With Hyperdiploid ( > 50 chromosomes ) B-Lineage Acute Lymphoblastic Leukemia : A Pediatric Oncology Group Study

Hyperdiploidy (>50 chromosomes, or a DNA index >1.16) confers a favorable prognosis in B-lineage acute lymphoblastic leukemia of childhood. Children with B-lineage acute lymphoblastic leukemia whose lymphoblasts at diagnosis accumulate high levels of methotrexate (MTX) and MTX polyglutamates (MTXPGs) in vitro experience a better eventfree survival than those whose lymphoblasts do not (Blood 76:44, 1990). Lymphoblasts from 13 children with hyperdiploidy (>50 chromosomes) accumulated high levels of MTXPGs (1,095 and 571 t o 2,346 pmol/lO9 cells [median and 25% to 75% intraquartile range]). These levels were higher than those in B-lineage lymphoblasts from 19 children with other aneuploidy (326 and 159 t o 775 pmol/lOg cells) and 15 children with diploidy (393 and 204 to 571 pmol/109 cells) (P = .0015). Chromosomal trisomies in hyperdiploid cases

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