ALL-TRANS-RETINOIC ACID POTENTIATES MEGAKARYOCYTE COLONY FORMATION - IN-VITRO AND IN-VIVO EFFECTS AFTER ADMINISTRATION TO ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS

In this study, we evaluated the in vitro growth of normal hematopoieti c progenitors (CFU-GM, BFU-E, CFU-GEMM, CFU-meg) stimulated by optimal sources of colony stimulating activity in the absence or presence of 10(-6) M all-trans retinoic acid (ATRA). ATRA alone did not show any c olony-stimulating ability when added in culture to partially purified bone marrow populations. On the other hand, it significantly increased the number of CFU-GM (p=0.003) and both the number (p=0.009) and size (p=0.002) of CFU-meg in the presence of appropriate colony-stimulatin g activity. Since ATRA had only modest stimulatory effects on purified CD34(+) cells, the megakaryocyte colony-stimulating activity of ATRA was mainly due to an increased production of endogenous cytokines by b one marrow accessory cells. In parallel experiments, the in vitro grow th of the different hematopoietic progenitors was evaluated in 28 pati ents affected by acute non-lymphoid leukemia (ANLL), mainly acute prom yelocytic leukemia (APL). Bone marrow cells were harvested after remis sion induction obtained: (i) in ten APL patients treated with ATRA fol lowed by one chemotherapy cycle (CHT) (3/7: Daunorubicin + Ara-C): gro up A ('ATRA/CHT'); (ii) eight APL patients treated with one CHT cycle alone (3/7 as above): group B ('APL-CHT'); (iii) in ten ANLL-non-APL p atients after one CHT cycle (3/7 as above): group C ('ANLL-CHT'). The number of the different hematopoietic progenitors, and in particular C FU-GM and CFU-meg, was significantly higher in APL patients treated wi th ATRA plus CHT (group A) compared to APL (group B) or ANLL-non-APL ( group C) patients treated with CHT alone (CFU-GM: p=0.01; CFU-meg: p=0 .03). Our data demonstrate that ATRA is able to potentiate both normal and APL megakaryocytopoiesis and suggest that the in vivo administrat ion of ATRA could be beneficial in other pathological conditions, wher e the megakaryocyte progenitor cell compartment is impaired.