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Upregulation of AKR1C1 in mesenchymal stromal cells promotes the survival of acute myeloid leukaemia cells
Author(s) -
Jiang Yajing,
Li Ying,
Cheng Jingying,
Ma Jiao,
Li Qinghua,
Pang Tianxiang
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16253
Subject(s) - mesenchymal stem cell , adipogenesis , cancer research , myeloid leukemia , bone marrow , stromal cell , downregulation and upregulation , myeloid , gene knockdown , leukemia , biology , cell culture , immunology , medicine , microbiology and biotechnology , gene , biochemistry , genetics
Summary The leukaemic bone marrow microenvironment, comprising abnormal mesenchymal stromal cells (MSCs), is responsible for the poor prognosis of acute myeloid leukaemia (AML). Therefore, it is essential to determine the mechanisms underlying the supportive role of MSCs in the survival of leukaemia cells. Through in silico analyses, we identified a total of 271 aberrantly expressed genes in the MSCs derived from acute myeloid leukemia (AML) patients that were associated with adipogenic differentiation, of which aldo‐keto reductase 1C1 ( AKR1C1 ) was significantly upregulated in the AML‐MSCs. Knockdown of AKR1C1 in the MSCs suppressed adipogenesis and promoted osteogenesis, and inhibited the growth of co‐cultured AML cell lines compared to the situation in wild‐ type AML‐derived MSCs. Introduction of recombinant human AKR1C1 in the MSCs partially alleviated the effects of AKR1C1 knockdown. In addition, the absence of AKR1C1 reduced secretion of cytokines such as MCP‐1, IL‐6 and G‐CSF from the MSCs, along with inactivation of STAT3 and ERK1/2 in the co‐cultured AML cells. AKR1C1 is an essential factor driving the adipogenic differentiation of leukaemic MSCs and mediates its pro‐survival effects on AML cells by promoting cytokine secretion and activating the downstream pathways in the AML cells.