Aclarubicin induces differentiation of leukemic progenitors in myelodysplastic syndrome cooperating with granulocyte colony-stimulating factor

We have reported that low-dose aclarubicin (ACR) therapy is effective in so me patients with myelodysplastic syndrome (MDS). Here, we demonstrate that a low concentration of ACR induces the in vitro differentiation of leukemic progenitor cells from patients with MDS. ACR (0.1 ng/ml) significantly inc reased the number of granulocyte colony-stimulating factor (G-CSF)-dependen t colonies from circulating blast cells in vitro in six out of seven MDS pa tients with refractory anemia with excess of blast in transformation or chr onic myelomonocytic leukemia, but not in all four patients with primary acu te myelogenous leukemia. In these MDS patients, the effect of ACR gradually disappeared along with the progression of MDS. Interestingly, the majority of G-CSF/ACR-dependent colonies consisted of rather differentiated myeloid cells such as myelocytes and metamyelocytes, whereas colonies formed by G- CSF alone were composed mainly of immature blastic cells. The number of G-C SF-responding progenitors significantly increased during a 24-48 h incubati on with ACR alone. The circulating blasts in MDS patients expressed G-CSF r eceptors at unchanged levels before and after the incubation with ACR. It i s suggested that ACR might increase clonogenic progenitor responsiveness to G-CSF in MDS, probably through modulating downstream signaling cascades as sociated with G-CSF receptors, and induce these progenitors to differentiat e in response to C-CSF. (C) 2000 Elsevier Science Ltd. All rights reserved.