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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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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Erythropoiesis
Myelodysplastic Syndromes
Erythroblasts
Leukemia, Myelomonocytic, Chronic
Erythrocytes
Bone Marrow
Neoplasms
Anemia
Mutation
Fetal Blood
Blood Cells
Homeostasis
Spleen
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

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

ASXL1 plays an important role in erythropoiesis. / Shi, Hui; Yamamoto, Shohei; Sheng, Mengyao; Bai, Jie; Zhang, Peng; Chen, Runze; Chen, Shi; Shi, Lihong; Abdel-Wahab, Omar; Xu, Mingjiang; Zhou, Yuan; Yang, Feng-Chun.

In: Scientific Reports, Vol. 6, 28789, 29.06.2016.

Research output: Contribution to journalArticle

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, vol. 6, 28789. https://doi.org/10.1038/srep28789
Shi H, Yamamoto S, Sheng M, Bai J, Zhang P, Chen R et al. ASXL1 plays an important role in erythropoiesis. Scientific Reports. 2016 Jun 29;6. 28789. https://doi.org/10.1038/srep28789
Shi, Hui ; Yamamoto, Shohei ; Sheng, Mengyao ; Bai, Jie ; Zhang, Peng ; Chen, Runze ; Chen, Shi ; Shi, Lihong ; Abdel-Wahab, Omar ; Xu, Mingjiang ; Zhou, Yuan ; Yang, Feng-Chun. / ASXL1 plays an important role in erythropoiesis. In: Scientific Reports. 2016 ; Vol. 6.
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