Open AccessThe role of E2A in ATPR‐induced cell differentiation and cycle arrest in acute myeloid leukaemia cells
Author(s) -
Zhang Meiju,
Wang Longfei,
Xu Xiaoling,
Du Yan,
Li Lanlan,
Deng Ge,
Feng Yubin,
Ou Ziyao,
Wang Ke,
Xu Yayun,
Peng Xiaoqing,
Chen Feihu
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17166
Subject(s) - retinoic acid , cell cycle , gene silencing , myeloid , cell cycle checkpoint , cell growth , cancer research , tretinoin , cell culture , cellular differentiation , biology , cell , gene , biochemistry , genetics
Acute myeloid leukaemia (AML) is a biologically heterogeneous disease with an overall poor prognosis; thus, novel therapeutic approaches are needed. Our previous studies showed that 4‐amino‐2‐trifluoromethyl‐phenyl retinate (ATPR), a new derivative of all‐trans retinoic acid (ATRA), could induce AML cell differentiation and cycle arrest. The current study aimed to determine the potential pharmacological mechanisms of ATPR therapies against AML. Our findings showed that E2A was overexpressed in AML specimens and cell lines, and mediate AML development by inactivating the P53 pathway. The findings indicated that E2A expression and activity decreased with ATPR treatment. Furthermore, we determined that E2A inhibition could enhance the effect of ATPR‐induced AML cell differentiation and cycle arrest, whereas E2A overexpression could reverse this effect, suggesting that the E2A gene plays a crucial role in AML. We identified P53 and c‐Myc were downstream pathways and targets for silencing E2A cells using RNA sequencing, which are involved in the progression of AML. Taken together, these results confirmed that ATPR inhibited the expression of E2A/c‐My c , which led to the activation of the P53 pathway, and induced cell differentiation and cycle arrest in AML.