目的：探讨PML::RARα融合蛋白对白介素6受体（interleukin-6 receptor ，IL-6R）的调控机制,及IL-6R对急性早幼粒细胞白血病（acute promyelocytic leukemia，APL）细胞增殖和分化的影响。方法：采用GSE12662和GSE10358数据集分析APL细胞中IL-6R的表达水平；采用逆转录实时定量PCR（reverse transcription quantitative real-time PCR，RT-qPCR）检测全反式维A酸（all-trans retinoic acid，ATRA）处理前后的NB4细胞及Zn²⁺诱导前后PR9细胞中IL-6R的mRNA表达；通过染色质免疫共沉淀（chromatin immunoprecipitation，ChIP）-seq数据分析、ChIP-qPCR实验及双荧光素酶报告基因活性检测，研究PML::RARα对IL-6R的调控机制；构建IL-6R过表达质粒并通过逆转录病毒转染至NB4细胞，利用细胞计数试剂盒-8（cell counting kit-8，CCK-8）实验检测细胞增殖，流式细胞术检测NB4细胞的分化情况。结果：GSE12662数据集分析结果显示，APL患者早幼粒细胞中IL-6R的表达水平（12.20±0.41）显著低于正常早幼粒细胞（13.14±0.47,t=4.289,P<0.001）和中性粒细胞（14.82±0.40,t=12.35,P<0.001）；GSE10358数据集分析结果显示,APL患者白血病细胞中IL-6R表达水平（5.93±0.84）显著低于非APL急性髓系白血病（acute myeloid leukemia，AML）患者（6.50±0.87,t=3.91,P<0.001）。APL患者细胞中IL-6R表达受PML::RARα融合蛋白的抑制，在APL中呈低表达模式，其机制为PML::RARα直接结合在IL-6R启动子区域，从而抑制其转录。在APL细胞株NB4中过表达IL-6R后，细胞增殖显著被抑制，转染4 d后，CCK-8检测到的吸光度值分别为0.86 ± 0.01和0.40 ± 0.01（t=32.66，P<0.001）；同时细胞分化显著增强，CD11b阳性细胞比例由（3.10±1.22）%升高至（14.4±1.11）%（t=11.84，P<0.001）。结论：IL-6R是PML::RARα的靶基因，PML::RARα通过直接结合IL-6R启动子抑制其转录；明确IL-6R通过抑制APL细胞增殖并诱导其部分分化发挥其生物学功能。

Objective To investigate the regulatory mechanism of PML::RARα fusion protein on interleukin-6 receptor (IL-6R) and the effects of IL-6R on the proliferation and differentiation of acute promyelocytic leukemia (APL) cells.Methods The expression levels of IL-6R in APL cells were analyzed using the GSE12662 and GSE10358 datasets. Reverse transcription quantitative real-time quantitative PCR（RT-qPCR） was performed to detect IL-6R mRNA expression in NB4 cells before and after all-trans retinoic acid (ATRA) treatment, as well as in PR9 cells before and after Zn²⁺ induction. Chromatin immunoprecipitation (ChIP)-seq data analysis, ChIP-qPCR experiments, and luciferase reporter gene activity assays were performed to explore the regulatory mechanism of PML::RARα on IL-6R. An IL-6R expression plasmid was constructed for NB4 cells via retrovirus. Cell proliferation was assessed using the cell counting kit-8 (CCK-8) assay, and CD11b expression was detected by flow cytometry.Results Analysis of the GSE12662 dataset revealed that the expression level of IL-6R in APL cells (12.20 ± 0.41) was significantly lower than that in normal promyelocytes (13.14 ± 0.47, t = 4.289, P < 0.001) and polymorphonuclear cells (14.82 ± 0.40, t = 12.35, P < 0.001). Moreover, analysis of the GSE10358 dataset showed that IL-6R expression in APL patients (5.93 ± 0.84) was significantly lower than that in non-APL AML patients (6.50 ± 0.87, t = 3.91, P < 0.001). PML::RARα directly bound to the promoter region of IL-6R to inhibit its transcriptional activity resulting in the low expression. Overexpression of IL-6R in the APL-derived NB4 cells significantly inhibited cell proliferation. Four days after transfection, the optical density values measured by the CCK-8 assay were 0.86 ± 0.01 and 0.40 ± 0.01, respectively (t = 32.66, P < 0.001). Simultaneously, cell differentiation was significantly enhanced. The ratio of the CD11b positive cells increased from 3.10 % ± 1.22 % to 14.4 % ± 1.11 % (t = 11.84, P < 0.001).Conclusions IL-6R is a target gene of PML::RARα, demonstrating that PML::RARα can suppress IL-6R transcription by binding to its promoter region. It is illustrated that IL-6R inhibited the cell proliferation and induced partial differentiation in APL cells.