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.
Publication types
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Case Reports
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adolescent
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Bone Marrow / pathology
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Drug Resistance, Neoplasm
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Female
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Hematopoietic Stem Cells / metabolism
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Hematopoietic Stem Cells / pathology
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Humans
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Infant
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Injections, Spinal
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Leukemia, Megakaryoblastic, Acute / drug therapy*
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Leukemia, Megakaryoblastic, Acute / metabolism
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Leukemia, Megakaryoblastic, Acute / pathology
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Leukemia, Myeloid, Acute / drug therapy*
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Male
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Methotrexate / administration & dosage
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Methotrexate / analogs & derivatives*
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Methotrexate / analysis
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Methotrexate / pharmacokinetics*
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Methotrexate / therapeutic use*
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Polyglutamic Acid / analogs & derivatives*
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Polyglutamic Acid / analysis
Substances
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Polyglutamic Acid
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methotrexate polyglutamate
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Methotrexate