Ku蛋白质在急、慢性骨髓系白血病的表达及其意义

Ku Protein Expression in Acute and Chronic Myeloid Leukemia and Its Significance

目的 本课题是研究在患有急性髓细胞白血病(acute myelocytic leukemia,AML)、急性淋巴细胞白血病(acute lymphoblastic leukemia, ALL)和慢性骨髓系白血病(chronic myelogenous leukemia, CML)患者中Ku蛋白的表达情况,为急慢性白血病的诊断和治疗提供有利临床应用价值。方法 选取2020年3月—2021年3月齐齐哈尔医学院附属第二医院收治的35例急性白血病患者周边血液与骨髓穿刺液,其中19例AML,16例ALL,另外,筛选BCR-ABL(+)CML的患者6例;对照组为12名正常人的周边血或骨髓穿刺液。在K562、HL-60、NB4细胞中转染Ku蛋白,利用实时定量PCR、流式细胞术鉴定Ku蛋白的基因表达;通过ELISA方法和Western blotting方法检测急慢性白血病中Ku蛋白的表达定位以及表达含量情况。应用米托司汀药物治疗前后对K562、HL-60、NB4细胞的增殖、凋亡、迁移、自噬等检测结果。结果 在所有急性白血病患者、AML、ALL的Ku70与Ku80表现,差异有统计学意义(P=0.001、0.036、0.046)。结论 延缓慢性白血病的发生、维护染色体结构完整性,防治染色体损伤而提供科学依据,为防治阻止DNA突变提供切实可行的分子诊断手段;同时对扩展急慢性白血病的放化疗治疗方案,制订个体化治疗措施具有重要意义。

Objective The aim of this study was to investigate the expression of Ku protein in patients suffering from acute myeloid leukemia(AML), acute lymphoblastic leukemia(ALL) and chronic myeloid leukemia(CML), to provide favorable clinical application value for the diagnosis and treatment of acute and chronic leukemia. Methods From March 2020 to March 2021, peripheral blood and bone marrow aspiration fluid were selected from 35 patients with acute leukemia admitted to the Second Affiliated Hospital of Qiqihar Medical College. Among them, 19 had acute myeloid leukemia and 16 had acute lymphoblastic leukemia. In addition, 6 patients with BCR-ABL(+) chronic myeloid leukemia were screened. The control group was peripheral blood or bone marrow aspirate from 12 normal subjects. Ku protein was transfected in K562, HL-60, and NB4 cells, and the gene expression of Ku protein was identified using real-time quantitative PCR and flow cytometry. The localization of Ku protein expression and the expression content in acute and chronic leukemia were detected by ELISA method and Western blotting method. The results of proliferation, apoptosis, migration and autophagy of K562, HL-60 and NB4 cells before and after the application of mitostatin drug treatment. Results Ku70 and Ku80 expression in all acute leukemia patients, acute myeloid leukemia, and acute lymphoblastic leukemia, the difference was statistically significant(P=0.001,0.036,0.046). Conclusion To delay the occurrence of chronic leukemia, maintain the structural integrity of chromosomes, prevent chromosomal damage and provide a scientific basis for prevention and treatment to stop DNA mutation and provide a practical molecular diagnostic tool. It is also important to expand the radiotherapy treatment plan for acute and chronic leukemia and to develop individualized treatment measures.