ASXL1 plays an important role in erythropoiesis

Hui Shi, Shohei Yamamoto, Mengyao Sheng, Jie Bai, Peng Zhang, Runze Chen, Shi Chen, Lihong Shi, Omar Abdel-Wahab, Mingjiang Xu, Yuan Zhou, Feng Chun Yang

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20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number28789
JournalScientific reports
Volume6
DOIs
StatePublished - Jun 29 2016

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    Shi, H., Yamamoto, S., Sheng, M., Bai, J., Zhang, P., Chen, R., Chen, S., Shi, L., Abdel-Wahab, O., Xu, M., Zhou, Y., & Yang, F. C. (2016). ASXL1 plays an important role in erythropoiesis. Scientific reports, 6, [28789]. https://doi.org/10.1038/srep28789