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 (CBL?E8/9) in several MDS patients with RUNX1 mutations. The CBL?E8/9/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. Overall design: Expression profiles of mRNA in HSC/Ps and Ly6G+ myeloid cells from CBL/RUNX1 mutants mice and their control mice.

骨髓增生异常综合征（MDS）以无效造血导致的骨髓（BM）衰竭为特征。然而，伴随克隆性扩增与细胞死亡加速的无效造血的潜在机制仍有待阐明。近期，我们在多例携带RUNX1突变的MDS患者中检测到CBL外显子8/9缺失突变（CBLΔE8/9）。构建的CBLΔE8/9/RUNX1S291fs小鼠（简称CR小鼠）呈现出多种MDS表型，包括全血细胞减少、发育异常以及骨髓无效造血。对造血干细胞/祖细胞（HSC/P）与突变型成熟髓系骨髓细胞进行RNA测序（RNA-Seq）分析显示，CR小鼠中诱导的基因表达特征与伴骨髓衰竭的MDS患者相似。其中，先天免疫相关基因的表达失调尤为显著。整体实验设计：对CBL/RUNX1突变小鼠及其对照小鼠的造血干细胞/祖细胞与Ly6G+髓系细胞的mRNA表达谱进行检测。