Lenalidomide and Dexamethasone Promote Erythropoiesis in Both Normal and RPS14 and RPS19 shRNA Infected Human CD34+ Cells: Implications for Therapy of Myelodysplastic Syndrome and Diamond-Blackfan Anemia.

Abstract 1092

Poster Board I-114

Lenalidomide, a derivative of thalidomide, induces erythroid responses in patients with myelodysplastic syndrome while dexamethasone induces erythroid responses in patients with Diamond Blackfan anemia. In vitro, both lenalidomide and dexamethasone have been shown to stimulate erythropoiesis. In the present study, we explored the activity of lenalidomide and dexamethasone in stimulating erythroid differentiation of primary hematopoietic progenitor cells and CD34+ cells expressing RPS19 or RPS14 shRNAs. Both agents increase the absolute number of erythroid cells produced from normal human CD34+ bone marrow cells by 1.3 to 1.6-fold. Importantly, both lenalidomide and dexamethasone increased the diminished erythroid proliferative capacity of CD34+ cells expressing either RPS19 or RPS14 shRNAs. However, the drugs have distinct effects on the production of erythroid progenitor colonies, Blast Forming Units – Erythroid (BFU-E) and Colony Forming Units – Erythroid (CFU-E). Dexamethasone caused a dose-dependent and statistically significant increase in the number of BFU-E colonies by 2-fold, while it had little effect on CFU-E. In marked contrast, lenalidomide caused a dose-dependent and statistically significant increase in the number of CFU-E colonies by 2.5-fold but had no effect on BFU-E colonies. In addition, the combination of lenalidomide and dexamethasone had an additive effect on the production of erythroid cells and on erythroid colony formation. Our findings imply that lenalidomide and dexamethasone regulate different stages of erythropoiesis and lend support to the concept that combination therapy may be effective in minimizing the potential toxicity of these two drugs in the clinical management of patients. These findings have important implications for the treatment of patients with Myelodysplastic Syndrome as well as with Diamond Blackfan Anemia.