Open AccessASXL1 plays an important role in erythropoiesis
Author(s) -
Hui Shi,
Shohei Yamamoto,
Mengyao Sheng,
Jie Bai,
Peng Zhang,
Runze Chen,
Shi Chen,
Lihong Shi,
Omar AbdelWahab,
Mingjiang Xu,
Yuan Zhou,
Feng Yang
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep28789
Subject(s) - erythropoiesis , bone marrow , ineffective erythropoiesis , myelodysplastic syndromes , chronic myelomonocytic leukemia , haematopoiesis , myeloid , cd34 , gene knockdown , biology , cancer research , erythropoietin , anemia , immunology , medicine , endocrinology , gene , stem cell , microbiology and biotechnology , genetics
ASXL1 mutations are found in a spectrum of myeloid malignancies with poor prognosis. Recently, we reported that Asxl1 +/ − mice develop myelodysplastic syndrome (MDS) or MDS and myeloproliferative neoplasms (MPN) overlapping diseases (MDS/MPN). Although defective erythroid maturation and anemia are associated with the prognosis of patients with MDS or MDS/MPN, the role of ASXL1 in erythropoiesis remains unclear. Here, we showed that chronic myelomonocytic leukemia (CMML) patients with ASXL1 mutations exhibited more severe anemia with a significantly increased proportion of bone marrow (BM) early stage erythroblasts and reduced enucleated erythrocytes compared to CMML patients with WT ASXL1 . Knockdown of ASXL1 in cord blood CD34 + cells reduced erythropoiesis and impaired erythrocyte enucleation. Consistently, the BM and spleens of VavCre + ; Asxl1 f/f ( Asxl1 ∆/∆ ) mice had less numbers of erythroid progenitors than Asxl1 f/f controls. Asxl1 ∆/∆ mice also had an increased percentage of erythroblasts and a reduced erythrocyte enucleation in their BM compared to littermate controls. Furthermore, Asxl1 ∆/∆ erythroblasts revealed altered expression of genes involved in erythroid development and homeostasis, which was associated with lower levels of H3K27me3 and H3K4me3. Our study unveils a key role for ASXL1 in erythropoiesis and indicates that ASXL1 loss hinders erythroid development/maturation, which could be of prognostic value for MDS/MPN patients.