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.

中文翻译：

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AKR1C1在间充质基质细胞中的上调促进了急性髓细胞性白血病细胞的存活。

白血病骨髓微环境包括异常的间充质基质细胞（MSC），是造成急性髓细胞白血病（AML）预后不良的原因。因此，至关重要的是确定在白血病细胞存活中MSC支持作用的潜在机制。通过计算机分析，我们在急性髓细胞性白血病（AML）患者的脂肪干细胞中共鉴定了271个异常表达基因，这些基因与成脂分化有关，其中ALD-酮还原酶1C1（AKR1C1）明显上调MSC。与野生型AML来源的MSC相比，在MSC中敲除AKR1C1抑制了脂肪形成并促进了成骨作用，并抑制了共培养的AML细胞系的生长。将重组人AKR1C1引入MSC中可部分缓解AKR1C1敲低的影响。另外，AKR1C1的缺失减少了MSCs细胞因子如MCP-1，IL-6和G-CSF的分泌，同时在共培养的AML细胞中也使STAT3和ERK1 / 2失活。AKR1C1是驱动白血病白血病MSCs成脂分化的重要因素，并通过促进细胞因子分泌和激活AML细胞的下游途径介导其对AML细胞的生存前效应。