title: Increased methotrexate polyglutamylation in acute megakaryocytic leukemia (M7) compared to other subtypes of acute myelocytic leukemia.
abstract: Acute myelocytic leukemia (AML) is a malignancy that is intrinsically resistant to methotrexate (MTX). AML blasts, when incubated with radiolabeled MTX, form lower amounts of long chain polyglutamates compared to acute lymphocytic leukemia (ALL) blasts, thus providing an explanation for their lack of responsiveness to MTX. Leukemic blasts obtained from two children with acute megakaryocytic leukemia (M7 subtype) when incubated with radiolabeled MTX showed increased accumulation of total as well as long chain MTX polyglutamates, comparable to levels previously demonstrated in another subtype of AML, acute monocytic leukemia (M5), as well as in blasts from patients with pre-B ALL. We suggest that M7-AML patients with blasts showing increased MTX polyglutamylation might benefit from treatment with MTX.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Argiris
authors.forename: G S
authors.initials: GS
authors.lastname: Longo
authors.forename: R
authors.initials: R
authors.lastname: Gorlick
authors.forename: W
authors.initials: W
authors.lastname: Tong
authors.forename: P
authors.initials: P
authors.lastname: Steinherz
authors.forename: J R
authors.initials: JR
authors.lastname: Bertino
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D007947:Leukemia, Megakaryoblastic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate