Gene expression profile of HSC/Ps and mature myeloid cells in MDS mutant clone

MDS 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 detected CBL exon 8/9 deletion mutation (CBLΔE8/9) in several MDS patients with RUNX1 mutations. The CBLΔE8/9/RUNX1S291fs mice (CR-mice) developed a variety of MDS phenotypes, such as pancytopenia, dysplasia, and ineffective hematopoiesis in BM. RNA-Seq of HSC/progenitor (HSC/P) and mutant mature myeloid BM cells revealed that gene signature induced in the CR-mice is similar to that in MDS patients with BM failure. Especially, innate immune-related genes were significantly dysregulated. Expression profiles of mRNA in HSC/Ps and Ly6G+ myeloid cells from CBL/RUNX1 mutants mice and their control mice.