B7-H6在慢性粒细胞白血病患者外周血、骨髓组织中的表达及临床意义

Expression of B7-H6 in peripheral blood and bone marrow of patient with chronic myeloid leukemia and its clinical significance

目的探讨慢性粒细胞白血病(Myeloid leukemia, CML)外周血(Peripheral blood, PB)和骨髓单个核细胞(Bone marrow mononuclear cells, BMMCs)中B7-H6基因的表达,分析其与临床特征、预后的关系。方法选取本院2010年1月-2013年5月收治的120例CML患者为研究对象,采用实时定量聚合酶链反应(Real time PCR)方法检测治疗前,治疗3、6、12个月时B7-H6基因mRNA表达水平,分析其与临床病理因素及预后之间的关系。结果 CML患者PB、BMMCs中B7-H6基因mRNA表达水平均低于正常人群(P<0.05)。与治疗前比较,治疗3、6、12个月时患者PB中B7-H6 mRNA的表达水平升高(P<0.05),随着治疗时间的增加,B7-H6 mRNA的表达水平也逐渐升高(P<0.05)。BCR-ABL1/ABL≤0.1%,有完全细胞遗传缓解(CCR)患者BMMCs中B7-H6水平显著高于BCR-ABL1/ABL>0.1%患者(P<0.000 1)或无CCR患者(P=0.001)。BMMCs中B7-H6的表达水平与BCR-ABL1/ABL水平呈负相关(r=-0.260,P=0.005 7)。B7-H6基因高表达患者中位无进展生存率(PFS)(未达到,HR:0.06,95%CI=0.03~0.37)高于低表达患者(81个月,HR:15.58,95%CI=2.68~30.23)(P=0.000 4)。结论 B7-H6基因在CML患者PB、BMMCs中低表达,与BCR-ABL1融合基因数量和治疗反应性有关,可用于CML的预后、进展和疗效评价。

Objective To investigate the expression level of B7-H6 in peripheral blood and bone marrow of patient with chronic myeloid leukemia(CML), and to analyze its association with clinicopathological characteristics and prognosis. Methods A total of 120 CML patients from January 2010 to May 2013 were selected as study subjects. The expression of B7-H6 mRNA in CML peripheral blood and bone marrow pre-and 3-, 6-, 12-month-posttreatment was detected by quantitative real time PCR, and its correlation between prognosis and clinicopathological factors was analyzed. Results The expression level of B7-H6 mRNA in the PB, BMMCs of CML patients was lower than that of the normal population(P<0.05). B7-H6 mRNA in PB at 3-, 6-, 12-month-posttreatment increased as compared with that of pre-treatment(P < 0.05). As treatment time prolonged, the expression level of B7-H6 mRNA increased gradually(P < 0.05). B7-H6 levels in BM samples from CML with BCR-ABL1/ABL≤0.1%, CCR were significantly higher than that in patients with BCR-ABL1/ABL>0.1%(P<0.0001) or without CCR(P<0.001). The expression level of B7-H6 in BMMCs was negatively correlated with the BCR-ABL1/ABL level(r=–0.260, P<0.05). Signifiant difference in PFS was observed between patients with high expression level of B7-H6(not reached, HR: 0.06, 95% CI =0.03-0.37) and low expression level(81 months, HR:15.58, 95% CI =2.68-30.23) in BM(P<0.05). Conclusion The low expression of the B7-H6 gene in CML is correlated with BCR-ABL1 copy number and responsiveness to treatment, and monitoring of B7-H6 expression may be used to evaluate CML prognosis, progression and treatment efficacy.