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

17 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
Externally publishedYes

Fingerprint

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, FC 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.
@article{4632f9d6c929410d8825dcb1f2577d57,
title = "ASXL1 plays an important role in erythropoiesis",
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.",
author = "Hui Shi and Shohei Yamamoto and Mengyao Sheng and Jie Bai and Peng Zhang and Runze Chen and Shi Chen and Lihong Shi and Omar Abdel-Wahab and Mingjiang Xu and Yuan Zhou and Yang, {Feng Chun}",
year = "2016",
month = "6",
day = "29",
doi = "10.1038/srep28789",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - ASXL1 plays an important role in erythropoiesis

AU - Shi, Hui

AU - Yamamoto, Shohei

AU - Sheng, Mengyao

AU - Bai, Jie

AU - Zhang, Peng

AU - Chen, Runze

AU - Chen, Shi

AU - Shi, Lihong

AU - Abdel-Wahab, Omar

AU - Xu, Mingjiang

AU - Zhou, Yuan

AU - Yang, Feng Chun

PY - 2016/6/29

Y1 - 2016/6/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84976615168&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84976615168&partnerID=8YFLogxK

U2 - 10.1038/srep28789

DO - 10.1038/srep28789

M3 - Article

AN - SCOPUS:84976615168

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 28789

ER -