INV(16) ACUTE MYELOID-LEUKEMIA CELLS SHOW AN INCREASED SENSITIVITY TOCYTOSINE-ARABINOSIDE IN-VITRO

Karyotype represents the major independent prognostic factor for respo nse and remission duration in acute leukemia. In particular, it has be en reported that acute myeloid leukemia (AML) patients with inv(16) ab normality show a better prognosis, especially in case of treatment wit h high-dose Ara-C (HD Ara-C) containing regimens In this study we aime d at testing whether leukemic cells from patients showing the inv(lb) were more sensitive to Ara-C in vitro, compared to AML blasts from pat ients with normal karyotype or chromosomal abnormalities other than t( 15;17) or t(8;21). We analyzed blast cells from 30 patients who were d iagnosed and treated in our institution. The IC50 of Ara-C, as tested by the XTT colorimetric assay, was significantly lower in cases with i nv(16) (18.5+/-15.88 mu mol/l vs. 38+/-14.6 mu mol/l,in cases with oth er abnormalities, p=0.01). This result was confirmed by a higher incor poration of [H-3]-Ara-C into DNA (p=0.02 and p=0.001 compared to sampl es with normal and abnormal karyotype, respectively). All the same, Ar a-C induced apoptosis was significantly increased in cells from patien ts with inv(16). Our data suggest a possible interaction between the m olecular background of inv(16) and a modification of intracellular met abolism of Ara-C, and could thus I provide a rationale for HD-Ara-C-ba sed schedules for patients with inv(16) AML.