Role of ASXLI loss in biological functions of HEL cells
10.3969/j.issn.1001-1978.2021.08.005
- Author:
Xiao JIANG
1
;
Fang-Nan XIAO
1
;
Yi-Ning LIU
1
;
Ming-Ying ZHANG
1
;
Jia-Jia YUAN
1
;
Wen XING
1
;
Yuan ZHOU
1
Author Information
1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- Publication Type:Journal Article
- Keywords:
ASXLI;
CRISPR/ Cas9;
HEL cells;
JAK2xbm;
myeloproliferative neoplasms;
ruxolitinib
- From:
Chinese Pharmacological Bulletin
2021;37(8):1057-1062
- CountryChina
- Language:Chinese
-
Abstract:
Aim To reveal the underlying mechanisms of the co-occurrence of ASXLI and JAK2ymr mutation by using human leukemia cell line HEL that carried homozygous /4A2V617F mutation in the elucidation of the role of ASXLI loss of function mutation in myeloproliferative neoplasms, so as to provide an important model for investigating the role of ASXLI mutation in myeloproliferative neoplasms at the cellular level. Methods HEL cell line with ASXLI knockout ( HEL-AKO) was established by using CRISPR/Cas9-mediated gene editing. And a series experiments based were preformed to verify the effect of ASXLI on HEL cell proliferation, clone formation and chemosensitivity. Results HEL-AKO cell line was successfully established, confirmed by sequencing results. We found that the loss of ASXLI could inhibit proliferation and induce cell cycle arrest at the G2/M phase. The colony-form- ing capacity of HEL-AKO cells was also markedly inhibited. Moreover, the HEL-AKO had higher cloning efficiency than HEL Control after ruxolitinib treatment. Conclusions Loss of function of ASXLI has an impact on cell biological function of HEL. Therefore, HEL- AKO cell line can be used to further explore the biological contribution of concomitant ASXLI in /4A2V617F mutated MPN.
