Inv(16) acute myeloid leukemia cells show an increased sensitivity to cytosine arabinoside in vitro.
Karyotype represents the major independent prognostic factor for response and remission duration in acute leukemia. In particular, it has been reported that acute myeloid leukemia (AML) patients with inv(16) abnormality show a better prognosis, especially in case of treatment with high-dose Ara-C (HD Ara-C) containing regimens. In this study we aimed at testing whether leukemic cells from patients showing the inv(16) were more sensitive to Ara-C in vitro, compared to AML blasts from patients with normal karyotype or chromosomal abnormalities other than t(15;17) or t(8;21). We analyzed blast cells from 30 patients who were diagnosed and treated in our institution. The IC50 of Ara-C, as tested by the XTT colorimetric assay, was significantly lower in cases with inv(16) (18.5+/-15.88 micromol/l vs. 38+/-14.6 micromol/l,in cases with other abnormalities, p=0.01). This result was confirmed by a higher incorporation of [3H]-Ara-C into DNA (p=0.02 and p=0.001 compared to samples with normal and abnormal karyotype, respectively). All the same, Ara-C induced apoptosis was significantly increased in cells from patients with inv(16). Our data suggest a possible interaction between the molecular background of inv(16) and a modification of intracellular metabolism of Ara-C, and could thus provide a rationale for HD-Ara-C-based schedules for patients with inv(16) AML.
Tosi
P
P
Institute of Hematology and Medical Oncology L. and A. Seràgnoli, University of Bologna, Italy.
Visani
G
G
Ottaviani
E
E
Testoni
N
N
Pellacani
A
A
Tura
S
S
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16; D003561:Cytarabine / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D003561:Cytarabine