CXC趋化因子受体1/2在急性白血病中的异常表达及临床意义探析

Abnormal expression and clinical significance of CXC chemokine receptor 1/2 in acute leukemia

  • 摘要:
      背景  CXCR家族已成为恶性肿瘤领域的研究热点,积极寻找并探究与急性白血病(acute leukemia,AL)发生、发展及预后相关的CXCR家族成员,在抗白血病基础研究与临床诊疗中具有重要意义。
      目的  探索骨髓微环境中CXC趋化因子受体1/2(CXC chemokine receptor 1/2,CXCR1/2)在AL患者骨髓单个核细胞中的表达水平及其与AL患者临床特征、疗效及预后的关系,为寻找AL的治疗靶点和病情监测提供新方向。
      方法  收集2018年11月- 2020年12月福建医科大学附属协和医院86例初诊(new-diagnosed,ND) AL患者骨髓标本同时收集26例健康者标本,其中男性17例,女性9例,中位年龄36.5(范围:23 ~ 49)岁。采用qRT-PCR技术检测两组人群骨髓单个核细胞中CXCR1/2表达。以CXCR1/2中位表达水平(Expressionmedian)作为界值,将ND-AL患者分为CXCR1/2高表达组和低表达组,分析不同CXCR1/2表达水平与AL患者临床特征及指标之间的关系和临床意义。
      结果  86例ND-AL患者中,包括29例急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患者和57例急性髓系白血病(acute myeloid leukemia,AML)患者。AL组中CXCR1Md(IQR): 0.691(0.176 ~ 2.14) vs 0.278(0.088 ~ 0.613), P<0.05、CXCR2相对表达量Md (IQR):1.938(0.729 ~ 3.681) vs 0.419(0.079 ~ 1.268), P<0.01均高于健康对照组,AML组与ALL组的CXCR1/2相对表达量差异无统计学意义(P>0.05);CXCR1/2的高表达与AL不良临床特征和指标有关(P<0.05),易出现髓外浸润、复发难治等不良结局。
      结论  AL患者的CXCR1/2表达上调,其对于AL的病情监测有一定的参考价值。

     

    Abstract:
      Background  CXCR family has become a research hotspot in the field of malignant tumors. Actively searching and exploring CXCR family members that are closely related to the occurrence, development and prognosis of acute leukemia (AL) are of great practical significance in the basic research and clinical diagnosis and treatment of anti-leukemia.
      Objective  To explore the expression level of CXC chemokine receptor 1/2 (CXCR1/2) under bone marrow microenvironment in bone marrow mononuclear cells of patients with AL, and analyze the relationship between CXCR1/2 expression and clinical characteristics, curative effect and prognosis of AL patients, so as to provide a new direction for the therapeutic target and disease monitoring of AL.
      Methods  Bone marrow specimens from 86 newly-diagnosed (ND) AL patients from November 2018 to December 2020 in Fujian Medical University Union Hospital were collected, including 49 males and 37 females, with a median age of 48 years (range: 17-73 years); At the same time, 26 healthy samples were collected, including 17 males and 9 females, with a median age of 36.5 years (range: 23-49 years). And quantitative real-time polymerase chain reaction (qRT-PCR) technology was used to detect the expression level of CXCR1/2. Taking the median expression level of CXCR1/2 as the cut-off value, the ND-AL patients were divided into CXCR1/2 high expression group and low expression group, and the relationship between different CXCR1/2 expression levels and various clinical characteristics, indicators and clinical significance of AL patients were analyzed respectively.
      Results  Among the 86 ND-AL patients included in this study, there were 29 patients with acute lymphoblastic leukemia (ALL) and 57 patients with acute myeloid leukemia (AML). The relative expression levels of CXCR1(MdIQR: 0.691 0.176-2.140 vs 0.278 0.088-0.613, P<0.05) and CXCR2 (MdIQR: 1.938 0.729-3.681 vs 0.419 0.079-1.268, P<0.01) in the AL group were higher than those in the healthy control group; there was no significant difference in the relative expression of CXCR1/2 between the AML group and the ALL group (P>0.05). The high expression of CXCR1/2 was associated with adverse clinical features and indicators of AL (P<0.05), and was prone to have adverse outcomes such as extramedullary infiltration, relapse and refractory.
      Conclusion  CXCR1/2 is up-regulated in AL, which has important reference value for the disease detection of AL.

     

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