In vitro apoptotic response of freshly isolated chronic myeloid leukemia cells to all-trans retinoic acid and cytosine arabinoside

Chronic myeloid leukemia (CML) is a hematological malignancy resulting from clonal expansion and massive accumulation of leukemic myeloid cells that r etain differentiation and maturation capacity, Since CML cell accumulation has been related to apoptosis inhibition by the product of the BCR-ABL gene , attempts to eradicate leukemic cells would require therapeutic drugs able to overcome this inherent resistance. Here, we investigated in vitro the a poptotic effect of all-trans retinoic acid (ATRA) and cytosine arabinoside (ARA-C), employed alone, in combination or in sequence, on freshly isolated cells from 10 patients with chronic-phase CML. Our cell cultures showed th at both ATRA and ARA-C were able to induce apoptosis in CML cells, even if ARA-C resulted more effective than ATRA. The combined use of ATRA and ARA-C seemed to have only an additive effect while the sequential use did not sh ow any advantage. These in vitro observations indicate that ATRA and ARA-C may be effective in reducing CML cells th rough apoptosis induction, sugges ting that it could be worthwhile to examine ATRA and ARA-C combinations in the therapy of CML. Copyright (C) 2001 S. Karger AG, Basel.