首页|期刊导航|中国全科医学|骨髓瘤患者白细胞免疫球蛋白样受体B1和CD36及淋巴增强因子1水平升高的意义研究

骨髓瘤患者白细胞免疫球蛋白样受体B1和CD36及淋巴增强因子1水平升高的意义研究OA

Significance of Elevated Levels of Leukocyte Immunoglobulin-like Receptor B1,CD36,and Lymphatic Enhancer Factor 1 in Patients with Myeloma

中文摘要英文摘要

背景 多发性骨髓瘤(MM)是一种不可治愈的恶性浆细胞肿瘤,其特征为骨髓中浆细胞的克隆性增殖,伴高钙血症(C)、肾损害(R)、贫血(A)和骨质破坏(B)等CRAB症状.白细胞免疫球蛋白样受体B1(LILRB1)、CD36、淋巴增强因子 1(LEF-1)分别与肿瘤代谢异常和免疫逃逸、病情进展和耐药性密切相关.光学基因组图谱技术(OGM)可全面反映患者的细胞遗传学变化.目的 探讨肿瘤微环境中LILRB1、CD36、LEF-1与MM发病的关系.方法 选取 2023 年 12 月—2025 年 1 月在首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科住院的 MM 患者76 例,根据疾病状态分为活动性 MM(aMM 组,n=43)和反应性 MM(rMM 组,n=33);选取同期在本院体检中心体检且性别、年龄匹配的 24 例体检健康者作为血浆检测对照组(HC 组),23 例良性贫血患者作为骨髓浆检测对照组.采用酶联免疫吸附试验(ELISA)检测血浆和骨髓浆中 LILRB1、CD36 和 LEF-1 水平.绘制血浆和骨髓浆 LILRB1、CD36 和 LEF-1 诊断 MM 的受试者工作特征(ROC)曲线,并根据截断值将患者分为高表达组和低表达组.对患者进行随访,随访截止时间为 2025 年 3 月,记录无进展生存期(PFS)和总生存期(OS).应用 OGM 对其中 6 例 MM 患者进行细胞遗传学异常检测.结果 aMM 组血浆 LILRB1、LEF-1 水平均高于 HC 组和 rMM 组(P<0.05);aMM 组骨髓浆 LILRB1、LEF-1 水平均高于良性贫血组和 rMM 组(P<0.05).aMM 组血浆 CD36 水平均高于 HC 组和 rMM 组(P<0.05).相关性分析显示,血浆中,LEF-1 与 LILRB1 呈正相关(rs=0.403,P=0.007),LEF-1 与 CD36 呈正相关(rs=0.340,P=0.017),LILRB1与CD36呈正相关(rs=0.406,P=0.006).骨髓浆中,LEF-1与LILRB1呈正相关(rs=0.528,P=0.001),LILRB1 与 CD36 呈正相关(rs=0.343,P=0.037),LEF-1 与 CD36 无相关性(rs=0.080,P=0.612).生存分析显示,血浆中,LILRB1、CD36 和 LEF-1 高表达组患者的 PFS、OS 均分别短于低表达组(P<0.05).骨髓浆中,LILRB1高表达组患者OS短于低表达组,LEF-1高表达组患者PFS、OS均分别短于低表达组(P<0.05).OGM检测显示,6 例 MM 患者中 3 例(50%)存在 17q12(HNF1β)缺失,且伴 del(17p)、t(4;14)等异常及 LEF-1 高表达,中位 PFS 和 OS 分别为 14 个月和 41 个月.结论 LILRB1、CD36 和 LEF-1 高表达与 MM 的疾病活动性、进展性及不良预后相关.LILRB1、CD36 可能通过脂质代谢调控与免疫抑制等方式参与 MM 疾病进程.对 6 例 MM 患者的 OGM 检测发现,50%的患者存在 17q12 缺失,导致 LEF-1 上游调控基因 HNF1β 表达异常,从而激活 Wnt 信号通路,进而促进MM发展.因此,LILRB1、CD36和LEF-1有望作为评估MM活动性、预测病情进展的生物标志物及潜在治疗靶点,为MM 治疗提供新思路.

Background Multiple myeloma(MM)is an incurable malignant plasma cell tumor characterized by clonal proliferation of plasma cells in the bone marrow,accompanied by CRAB symptoms such as elevated blood calcium(C),renal damage(R),anemia(A),and bone damage(B).Human leukocyte immunoglobulin like receptor B1(LILRB1)and CD36 are associated with metabolic abnormalities and immune evasion.Lymphatic enhancer factor 1(LEF-1)is closely related to tumorigenesis,disease progression,and drug resistance.Optical genome mapping(OGM)technology can comprehensively reflect the cytogenetic changes of patients.Objective To explore the relationship between changes of LILRB1,CD36 and LEF-1 in the tumor microenvironment and the onset of MM.Methods 76 MM patients who were hospitalized in the Department of Hematology and Oncology,Beijing Chao-yang Hospital,Capital Medical University from December 2023 to January 2025 were selected.They were divided into active MM(aMM group,n=43)and reactive MM(rMM group,n=33)based on their disease status.Meanwhile,24 healthy individuals who underwent physical examinations at the hospital during the same period and were matched in terms of gender and age were selected as the plasma detection control group(HC group),and 23 patients with benign anemia were selected as the bone marrow plasma detection control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of LILRB1,CD36,and LEF-1 in plasma and bone marrow plasma.Receiver operating characteristic(ROC)curves for plasma and bone marrow plasma LILRB1,CD36,and LEF-1 in diagnosing MM were plotted,and patients were divided into high-expression and low-expression groups based on the cut-off value.Follow-up was conducted for the patients until March 2025,and the progression-free survival(PFS)and overall survival(OS)were recorded.OGM was used to detect cytogenetic abnormalities in 6 MM patients.Results In the plasma,the levels of LILRB1 and LEF-1 in the aMM group were higher than those in the HC group and the rMM group(P<0.05);in the bone marrow plasma,the levels of LILRB1 and LEF-1 in the aMM group were higher than those in the benign anemia group and the rMM group(P<0.05).In the plasma,the level of CD36 in the aMM group was higher than that in the HC group and the rMM group(P<0.05).Correlation analysis showed that in plasma,LEF-1 was positively correlated with LILRB1(rs=0.403,P=0.007)and CD36(rs=0.340,P=0.017),and LILRB1 was positively correlated with CD36(rs=0.406,P=0.006).In bone marrow plasma,LEF-1 was positively correlated with LILRB1(rs=0.528,P=0.001),and LILRB1 was positively correlated with CD36(rs=0.343,P=0.037),whereas no correlation was observed between LEF-1 and CD36(rs=0.080,P=0.612).Survival analysis revealed that in plasma,patients with high expression of LILRB1,CD36,and LEF-1 had significantly shorter PFS and OS compared to those with low expression(P<0.05).In bone marrow plasma,patients with high LILRB1 expression had shorter OS,and those with high LEF-1 expression had shorter PFS and OS(P<0.05).OGM testing showed that 3 out of 6 MM patients(50%)had 17q12(HNF1β)deletion,accompanied by abnormalities such as del(17p),t(4;14),and high expression of LEF-1.The median PFS and OS were 14 months and 41 months,respectively.Conclusion The high expression of LILRB1,CD36 and LEF-1 is associated with disease activity,progression,and poor prognosis in MM.LILRB1 and CD36 may participate in the pathological process of MM through lipid metabolism regulation and immune suppression.OGM testing on 6 MM patients revealed that 50%of them had 17q12 deletion,leading to abnormal expression of HNF1β,an upstream regulatory gene of LEF-1,which activates the Wnt signaling pathway to promote MM development.Therefore,LILRB1,CD36,and LEF-1 are expected to serve as biomarkers and potential therapeutic targets for evaluating MM activity,predicting disease progression,and providing new ideas for MM treatment.

张天宇;黄仲夏;陈飞;李新;张佳佳;申曼;詹晓凯;汤然;范斯斌;赵凤仪

100038 北京市,首都医科大学附属北京世纪坛医院急危重症医学中心重症医学科||100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科100050 北京市,首都医科大学附属北京友谊医院血液内科100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科100043 北京市,首都医科大学附属北京朝阳医院石景山院区血液与肿瘤科

医药卫生

多发性骨髓瘤白细胞免疫球蛋白样受体B1CD36淋巴增强因子1光学基因组图谱HNF1β基因预后

Multiple myelomaLILRB1CD36LEF-1OGMHNF1β genePrognosis

《中国全科医学》 2026 (29)

4272-4280,9

北京市科技计划项目(Z171100000417010)北京市石景山区卫生与健康委员会医学重点学科建设项目(石卫健医发[2021]2号)

10.12114/j.issn.1007-9572.2025.0219

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