Effects of crizotinib on gene expression profiles of cultured hematopoietic stem and progenitor cells (HSPCs) derived from MDS mice

Myelodysplastic syndromes are characterized by bone marrow (BM) failure due to ineffective hematopoiesis. However, the underlying mechanisms of ineffective hematopoiesis, in which clonal expansion coexists with accelerated cell death, remain to be elucidated. Recently, we established the CBL?E8/9/RUNX1S291fs mice (MDS mice), which develope a variety of MDS phenotypes including defects in megakaryocyte (MK) maturation. We identified crizotinib as a potent inducer of MK maturation. RNA-Seq of cultured HSPCs derived from the mice revealed that crizotinib increased the expression levels of MK and platelet-related genes. Overall design: To investigate effects of crizotinib on gene expression profiles in megakaryocyte progenitors derived from MDS mice, MDS mice were generated. Hematopoietic stem and progenitor cells (HSPCs) were isolated from the mice, cultured in the presence of thrombopoietin, and treated with DMSO (dimethyl sulfoxide) or crizotinib for 48 h. Gene expression profiling analysis of RNA-seq data for DMSO-treated cells and crizotinib-treated cells was performed.