共刺激分子B7-H3在急性髓系白血病中的表达及生物学意义

Expression of costimulatory molecule B7-H3 on human acute myeloid leukemia and its biological significance

目的:检测共刺激分子B7-H3在初诊急性髓系白血病(human acute myeloid leukemia,AML)患者中的表达,探讨其临床意义。方法:应用流式细胞术(FCM)检测66例初诊AML患者原始幼稚细胞群上B7-H3分子膜蛋白的表达,RT-PCR技术检测B7-H3 m RNA产物的表达。分析B7-H3分子的表达与AML患者发病时年龄、性别、初诊时外周血白细胞计数以及染色体之间的关系,评估B7-H3分子的表达与患者的无进展生存期(progression-free survival,PFS)和总体生存期(overall survival,OS)之间的关系。结果:正常对照组B7-H3分子表达阴性。共刺激分子B7-H3在66例初诊AML患者中阳性表达率为42%(28/66)。在不同性别、年龄和白细胞分组中,B7-H3阳性率表达无统计学差异(P=0.924,0.541,0.310);预后差染色体变异组的B7-H3分子的阳性表达率明显高于预后好及中等预后组(P<0.001)。B7-H3分子阳性组患者的PFS(7.4个月vs.15.2个月)及OS(9.8个月vs.17.8个月)均明显低于阴性组患者(P<0.05)。此外,在AML-M2亚型中,预后差染色体变异组B7-H3分子的表达明显高于预后好及中等预后组(30.05%±23.10%vs.10.08%±7.07%,P<0.001),B7-H3与骨髓白血病细胞CD34存在共表达,并且CD34阳性组的B7-H3分子表达明显高于CD34阴性组(20.90%±19.70%vs.9.63%±7.21%,P=0.034)。结论:共刺激分子B7-H3的表达对于AML患者的病情进展有一定影响,B7-H3分子表达阳性的患者预后更差。B7-H3对AML的预后判断和指导临床治疗具有重要意义。

Objective：To analyze the expression of costimulatory molecule B7-H3 in patients with acute myeloid leukemia（AML）,and explore the clinical significance of the expression of B7-H3. Methods：The expression of B7-H3 protein was detected by flow cytometry（FCM）and the expression of B7-H3 m RNA was detected by RT-PCR. We analyzed the relationship between the expression of B7-H3 and some clinical factors. We evaluated the progression-free survival（PFS）and overall survival（OS）between the B7-H3 positive group and the B7-H3 negative group. Results：The results demonstrated that B7-H3 was weakly expressed on bone marrow of AML patients,and RT-PCR also detected m RNA of B7-H3. No B7-H3 positive cells were detected in the normal human bone marrow.B7-H3 was detected in 28 of the 66 cases（42%）. However,among 66 AML cases,no significantly higher frequency of B7-H3 positive cases was found in the male or female group（P=0.924）. Neither was observed between patients who were older than 60 years and those less than 60 years（P=0.541）. The B7-H3 positive expression was of no significant within the higher WBC subset（≥ 30×109/L）（P=0.310）. There was significant differences between favorable karyotype subset and unfavorable ones（P0.001）. There was also statistical difference in PFS（7.4 mon vs. 15.2 mon）and OS（9.8 mon vs. 17.8 mon）between the B7-H3 positive group and B7-H3 negative group,respectively（P〈0.05）. Furthermore,in the AML-M2 subtype,the expression of B7-H3 on the unfavorable karyotype group（8 cases）was higher than the favorable group（29 cases,30.05% ± 23.10% vs. 10.08% ± 7.07%,P0.001）. There was coexpression between B7-H3 and CD34 of blast cells. The expression of B7-H3 in the CD34 positive group was higher than that in the negative group（20.90% ± 19.70% vs. 9.63% ± 7.21%,P=0.034）. Conclusion：The expression of B7-H3 in AML has relationship with the expression of the karyotype. The B7-H3 positive patients have the worse prognostic. The research of B7-H3 may be a new prognostic marker and provide insights into the leukemogenesis of acute myeloid leukemia.