A possible role for methotrexate in the treatment of childhood acute myeloid leukaemia, in particular for acute monocytic leukaemia.
作者： M.G. Rots , R. Pieters , G. Jansen , G.J.L. Kaspers , C.H. Van Zantwijk
DOI: 10.1016/S0959-8049(00)00433-0
关键词:
摘要: Acute myeloid leukaemia (AML) is thought to be methotrexate (MTX)-resistant. However, a small study suggested that acute monocytic leukemia (AML-M5) sensitive MTX. We measured MTX accumulation/polyglutamylation in 20 AML-nonM5, 37 AML-M5 and 83 common/preB-acute lymphoblastic (c/preB-ALL) samples. Membrane transport was determined 11 childhood AMLs (including 3 AML-M5) 25 c/preB-ALL sensitivity 23 15 63 common/preB-ALL samples using the thymidylate synthase (TS) inhibition assay. higher AML compared with precluding defect AML. Accumulation of long-chain polyglutamates MTX-Glu(4-6) 3-fold lower for AML-nonM5 cells (median 268 versus 889 pmol MTX-Glu(4-6)/10(9) cells; P < or = 0.001); samples, median accumulation 0 pmol/10(9) (P 0.001). After short-term exposure, 6-fold more resistant (2.16 0.39 microM; 0.001), while 2-fold 0.02). In both cells, resistance circumvented by continuous exposure TSI(50) values: 0.052 0.041 microM, respectively) value 0.066 microM. conclusion, relatively other AML-subtypes even though polyglutamylation poor. Using were at least as cells. This report suggests might an overlooked drug treatment
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