Impaired polyglutamylation of methotrexate (MTX) and thus poor retenti
on is believed to be the basis of intrinsic resistance in blasts from
patients with acute myeloid leukemia (AML) to MTX. We studied addition
al samples from patients with this disease, and confirmed that polyglu
tamylation 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 accumu
late high levels of MTX polyglutamates and was relatively sensitive to
MTX, strengthening the concept that M5 blasts may be sensitive to thi
s drug. MTX may be an overlooked drug for the treatment of acute monoc
ytic leukemia.