慢性淋巴细胞白血病CD49d表达模式与分子遗传学和热点突变基因的相关性

The correlation of CD49d expression pattern with molecular genetics and hotspot gene mutants in patients with chronic lymphocytic leukemia

目的探索慢性淋巴细胞白血病患者CD49d表达模式与分子遗传学和热点突变基因的相关性。方法流式细胞术检测CD49d表达模式, 以单峰与双峰、阴性与阳性为分组依据。采用组合探针荧光原位杂交(FISH)进行分子遗传学分析, 二代测序(NGS)进行基因突变检测。结果 CD49d阳性患者43例(23.89%), CD49d阴性患者137例(76.11%), CD49d单峰表达患者96例(53.33%), CD49d双峰表达患者84例(46.67%)。与CD49d阴性组患者相比, CD49d阳性组患者Rai分期高(P=0.048), 脾脏增大比例高(P=0.030)。与CD49d单峰患者相比, CD49d双峰患者脾脏增大比例高(P=0.009)。CD49d双峰阴性组11q22-发生率显著高于单峰阴性组(24.29%对10.45%, P=0.043)。CD49d单峰组+12发生率高于双峰组(16.67%对5.95%, P=0.035), 单峰阳性组+12发生率高于双峰阴性组(17.24%对4.29%, P=0.045), 单峰阴性组+12发生率高于双峰阴性组(16.42%对4.29%, P=0.024)。CD49d阳性组BIRC3突变率高于CD49d阴性组(11.63%对2.92%, P=0.037)。结论 CD49d与11q22-、+12和BIRC3基因突变有显著的相关性, CD49d呈双峰表达与预后较差指标相关。

Objective To explore the correlation of CD49d expression patterns with molecular genetics and hotspot gene mutants in patients with chronic lymphocytic leukemia.Methods The expression of CD49d was detected by flow cytometry and grouped into homogeneous,bimodal,negative and positive expression.Panel fluorescence in situ hybridization(FISH)was used for molecular genetics analysis and next-generation sequencing(NGS)was conducted for gene mutation detection.Results There were 43 patients(23.89%)with positive CD49d expression,137 patients(76.11%)with negative CD49d expression,96 patients(53.33%)with homogeneous CD49d expression and 84 patients(46.67%)with bimodal CD49d expression.Compared with patients in the CD49d negative group,patients in the CD49d positive group had higher Rai stage(P=0.048)and higher proportion of spleen enlargement(P=0.030).Compared with patients with homogeneous expression of CD49d,patients with bimodal expression of CD49d had a higher proportion of spleen enlargement(P=0.009).The expression rate of 11q22-in bimodal CD49d-group was significantly higher than that in homogeneous CD49d-group(24.29%vs 10.45%,P=0.043).The incidence of+12 in homogeneous CD49d group was higher than that in bimodal CD49d group(16.67%vs 5.95%,P=0.035).The incidence of+12 in homogeneous CD49d+group was higher than that in bimodal CD49d-group(17.24%vs 4.29%,P=0.045).The incidence of+12 in homogeneous CD49d-group was higher than that in bimodal CD49d-group(16.42%vs 4.29%,P=0.024).BIRC3 mutation rate in CD49d positive group was higher than that in CD49d negative group(11.63%vs 2.92%,P=0.037).Conclusion There were significant correlations between CD49d and 11q22-,+12 and BIRC3 gene mutation.Patients with bimodal CD49d were more correlated with poor prognosis indexes.