<i>ROBO1</i> deficiency impairs HSPC homeostasis and erythropoiesis via <i>CDC42</i> and predicts poor prognosis in MDS.

ABSTRACT: Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a

SUBMITTER: Jin JC 

PROVIDER: S-EPMC12488054 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature