Acute monocytic leukemia: a myeloid leukemia subset that may be sensitive to methotrexate.
Impaired polyglutamylation of methotrexate (MTX) and thus poor retention is believed to be the basis of intrinsic resistance in blasts from patients with acute myeloid leukemia (AML) to MTX. We studied additional samples from patients with this disease, and confirmed that polyglutamylation of MTX was poor in ANLL blast cells. However, in one subset of ANLL, acute monocytic leukemia, (M5) leukemia blasts were found to be capable of accumulating and forming long-chain MTX polyglutamates. An acute monocytic leukemia cell line, THP-1 also was found to accumulate high levels of MTX polyglutamates and was relatively sensitive to MTX, strengthening the concept that M5 blasts may be sensitive to this drug. MTX may be an overlooked drug for the treatment of acute monocytic leukemia.
Göker
E
E
Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Kheradpour
A
A
Waltham
M
M
Banerjee
D
D
Tong
W P
WP
Elisseyeff
Y
Y
Bertino
J R
JR
D000328:Adult; D000368:Aged; D001692:Biological Transport; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000378:metabolism / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate