title: Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease.
abstract: We compared blast cells from adult and pediatric patients with untreated acute lymphoblastic leukemia (ALL) (as separated groups of T-lineage cell and B-lineage cell ALL) to determine if methotrexate (MTX) polyglutamate formation in adult patients might be a contributing cause to the known difference in clinical outcome, since MTX is a key drug in chemotherapy regimens. Adult B-lineage cell ALL blasts and blasts from the patients with T-lineage cell ALL accumulated lower amounts of total MTX and polyglutamates, especially long-chain MTX polyglutamates (glu3-6) than pediatric B-lineage cell ALL blasts. In view of the importance of polyglutamylation of MTX as a determinant of cytotoxicity of this drug, decreased formation of MTX polyglutamates is likely a contributing cause to the lower cure rate in adult ALL and T-lineage cell ALL as compared to childhood B-lineage cell ALL.
authors.affiliation: Department of Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: E
authors.initials: E
authors.lastname: Göker
authors.forename: J T
authors.initials: JT
authors.lastname: Lin
authors.forename: T
authors.initials: T
authors.lastname: Trippett
authors.forename: Y
authors.initials: Y
authors.lastname: Elisseyeff
authors.forename: W P
authors.initials: WP
authors.lastname: Tong
authors.forename: D
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: C
authors.initials: C
authors.lastname: Tan
authors.forename: P
authors.initials: P
authors.lastname: Steinherz
authors.forename: B I
authors.initials: BI
authors.lastname: Schweitzer
authors.forename: J R
authors.initials: JR
authors.lastname: Bertino
mesh_terms: D000328:Adult; D000367:Age Factors; D002648:Child; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D008727:Methotrexate / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D011099:Polyglutamic Acid; D008727:Methotrexate