中国全科医学 ›› 2025, Vol. 28 ›› Issue (27): 3391-3398.DOI: 10.12114/j.issn.1007-9572.2023.0541

• 论著 • 上一篇    下一篇

急性T淋巴细胞白血病β-肾上腺素受体的表达情况及临床意义研究

徐艳朋1,2, 黄佩2,3, 张平平3, 罗艳2,3, 施晓琪2,3, 吴柳松3, 陈艳2,3,*(), 何志旭2,3,*()   

  1. 1.563000 贵州省遵义市,遵义医科大学附属医院小儿外科
    2.563000 贵州省遵义市,遵义医科大学组织损伤修复与再生医学省部共建协同创新中心
    3.563000 贵州省遵义市,遵义医科大学附属医院儿科
  • 收稿日期:2023-08-01 修回日期:2024-07-03 出版日期:2025-09-20 发布日期:2025-07-22
  • 通讯作者: 陈艳, 何志旭

  • 作者贡献:

    徐艳朋进行论文构思、数据分析及统计、论文撰写等;黄佩协助指导论文设计;张平平、罗艳进行临床资料及数据收集;施晓琪、吴柳松进行试验;陈艳、何志旭负责文章审校、监督管理。

  • 基金资助:
    国家自然科学基金资助项目(82260036); 教育部协同创新中心建设项目(教科技厅函〔2020〕39号); 贵州省科技计划项目(黔科合基础-ZK[2024]一般300); 贵州省卫生健康委科学技术基金项目(gzwkj2025-086)

Expression of β-Adrenergic Receptors in Acute T-cell Lymphoblastic Leukemia and Its Clinical Significance

XU Yanpeng1,2, HUANG Pe2,3, ZHANG Pingping3, LUO Yan2,3, SHI Xiaoqi2,3, WU Liusong3, CHEN Yan2,3,*(), HE Zhixu2,3,*()   

  1. 1. Department of Pediatric Surgery, the Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China
    2. Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University, Zunyi 563000, China
    3. Department of Pediatrics, the Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China
  • Received:2023-08-01 Revised:2024-07-03 Published:2025-09-20 Online:2025-07-22
  • Contact: CHEN Yan, HE Zhixu

摘要: 背景 β-肾上腺素受体(β-AR)与部分肿瘤的发生、发展密切相关,但急性T淋巴细胞白血病(T-ALL)细胞上是否存在β-AR的表达,且β-AR是否与T-ALL的预后及危险度相关,目前国内外报道较缺乏。 目的 明确T-ALL患儿白血病细胞上β-AR的表达情况,并分析β-AR对T-ALL患儿危险度及预后的影响。 方法 数据库查询β1-AR、β2-AR及β3-AR在白血病细胞及其他恶性肿瘤上的表达水平,同时查询β1-AR、β2-AR及β3-AR的表达水平对肿瘤预后的影响,并归纳总结数据。收集2019年—2022年于遵义医科大学附属医院治疗的T-ALL患儿的临床资料及骨髓标本,共40例,根据诊治情况及疗效分为T-ALL初诊组及T-ALL缓解组,其中T-ALL初诊组23例,T-ALL缓解组17例;同时收集15例非血液疾病患儿的临床资料及骨髓标本作为对照组。将T-ALL初诊组患儿分为中危亚组(9例)及高危亚组(14例)。同时将T-ALL初诊组患儿按预后结果进行分组,死亡及复发者为预后不良亚组(10例),疗效好并完全缓解者为预后良好亚组(13例)。收集患儿的临床资料。采用免疫印迹试验(Western blot)检测T-ALL细胞β-AR表达。采用Pearson相关性分析或Spearman秩相关检验分析β-AR与T-ALL患儿危险程度的相关性。采用多因素Logistic回归分析探究T-ALL患儿高危的影响因素。 结果 数据库检索结果发现:β1-AR在前列腺癌中表达水平较高,β2-AR在血液及前列腺等相关恶性肿瘤中表达水平较高,β3-AR在恶性肿瘤中的表达水平极低。与正常血液组织比较,急性髓系白血病血液组织β-AR基因的表达较高,主要以β2-AR基因表达为主,其次是β1-AR基因,而β3-AR基因表达水平较低。β1-AR基因可影响宫颈癌、肺鳞状细胞癌、胰腺癌、肉瘤及黑色素瘤患者的生存率,β2-AR基因可影响肾癌、肺腺癌及胸腺癌患者的生存率,β3-AR基因可影响肾透明细胞癌患者的生存率。Western blot结果显示,T-ALL初诊组β1-AR、β2-AR、β3-AR蛋白表达水平高于对照组、T-ALL缓解组(P<0.05)。高危亚组β3-AR高于中危亚组(P<0.05)。多因素Logistic回归分析结果显示,β3-AR升高(OR=7.036,95%CI=1.244~39.783,P=0.027)及化疗15 d后骨髓中有白血病细胞(OR=10.667,95%CI=1.035~109.941,P=0.047)是T-ALL患儿高危的危险因素,β3-AR升高(OR=8.447,95%CI=1.557~45.819,P=0.013)是T-ALL患儿预后不良的危险因素。相关性分析结果显示,β2-AR与白血病计数、初诊骨髓白血病细胞比例、化疗15 d骨髓白血病细胞呈正相关,β3-AR与T-ALL患儿危险度、预后呈正相关(P<0.05)。 结论 T-ALL患儿白血病细胞上存在β-AR的异常高表达,且β-AR表达水平的下降可作为T-ALL患儿缓解的指标。此外,β3-AR异常高表达是T-ALL患儿发生高危及预后不良的独立危险因素。

关键词: 白血病,T细胞, β-肾上腺素受体, 儿童, 预后

Abstract:

Background

β-adrenergic receptors (β-AR) have been closely associated with the occurrence and progression of certain tumors. However, the expression of β-AR in acute T-cell lymphoblastic leukemia (T-ALL) and its correlation with the prognosis and risk stratification of T-ALL have not been reported domestically or internationally.

Objective

To clarify the expression of β-AR on the leukemic cells of pediatric T-ALL patients and to analyze the impact of β-AR on the risk stratification and prognosis of T-ALL patients.

Methods

Database searches were conducted to determine the expression levels of β1-AR, β2-AR, and β3-AR in leukemia and other malignant tumors, as well as the influence of their expression levels on tumor prognosis, with data summarized accordingly. Clinical data and bone marrow specimens were collected from 40 pediatric T-ALL patients treated at the Affiliated Hospital of Zunyi Medical University from 2019 to 2022, divided into newly diagnosed T-ALL group and T-ALL remission group based on diagnosis and therapeutic outcomes, with 23 and 17 cases respectively; 15 cases of clinical data and bone marrow specimens from pediatric patients with non-hematological diseases were collected as a control group. The newly diagnosed T-ALL group was further divided into intermediate-risk subgroup (9 cases) and high-risk subgroup (14 cases). Additionally, the newly diagnosed T-ALL group was categorized based on prognosis outcomes into a poor prognosis subgroup (10 cases) with death and relapse, and a good prognosis subgroup (13 cases) with good therapeutic effect and complete remission. Clinical data of the pediatric patients were collected. β-AR expression in T-ALL cells was detected using Western blot. Pearson correlation analysis or Spearman rank correlation test was used to explore the correlation between β-AR and the degree of risk in T-ALL pediatric patients. Multifactorial Logistic regression analysis was used to explore the risk factors for high risk in T-ALL pediatric patients.

Results

Database search results revealed that β1-AR has a higher expression level in prostate cancer, β2-AR has a higher expression level in hematological and prostate-related malignant tumors, and β3-AR has a very low expression level in malignant tumors. Compared with normal blood tissue, the expression of β-AR genes in acute myeloid leukemia blood tissue is higher, mainly dominated by β2-AR gene expression, followed by β1-AR gene, while the expression level of β3-AR gene is lower. The β1-AR gene can affect the survival rate of patients with cervical cancer, squamous cell carcinoma of the lung, pancreatic cancer, sarcoma, and melanoma; the β2-AR gene can affect the survival rate of patients with renal cell carcinoma, adenocarcinoma of the lung, and thymic carcinoma; the β3-AR gene can affect the survival rate of patients with renal clear cell carcinoma. Western blot results showed that the protein expression levels of β1-AR, β2-AR, and β3-AR in the newly diagnosed T-ALL group were higher than those in the control group and T-ALL remission group (P<0.05). The β3-AR in the high-risk subgroup was higher than that in the intermediate-risk subgroup (P<0.05). Multifactorial Logistic regression analysis showed that an increase in β3-AR (OR=7.036, 95%CI=1.244-39.783, P=0.027) and the presence of leukemic cells in the bone marrow after 15 days of chemotherapy (OR=10.667, 95%CI=1.035-109.941, P=0.047) are risk factors for high risk in T-ALL pediatric patients, and an increase in β3-AR (OR=8.447, 95%CI=1.557-45.819, P=0.013) is a risk factor for poor prognosis in T-ALL pediatric patients. Correlation analysis results showed that β2-AR is positively correlated with white blood cell count, the proportion of leukemic cells in the bone marrow at the first diagnosis, and the bone marrow leukemic cells after 15 days of chemotherapy, and β3-AR is positively correlated with the risk and prognosis of T-ALL pediatric patients (P<0.05) .

Conclusion

There is an abnormally high expression of β-AR on the leukemic cells of T-ALL pediatric patients, and the decrease in the expression level of β-AR can be used as an indicator of remission in T-ALL pediatric patients. In addition, the abnormally high expression of β3-AR is an independent risk factor for the occurrence of high risk and poor prognosis in T-ALL pediatric patients.

Key words: Leukemia, T-cell, β-adrenergic receptor, Child, Prognosis