慢性淋巴细胞白血病患者的临床和分子遗传学研究

Molecular cytogenetic and clinical study of chronic lymphocytic leukemia

目的:探讨荧光原位杂交技术(fluorescence in situ hybridization,FISH)在检测慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)中的应用及与患者临床指标和特征的相关性,并分析其判断患者预后的价值。方法:收集2013年6月—2020年10月初诊于南通大学附属医院CLL患者74例,男43例,女31例。收集患者相关的临床特征、实验室检查、骨髓涂片、免疫分型及FISH结果等资料。分析FISH检测的分子遗传学异常与患者的性别、年龄、临床Binet分期、Rai分期及相关实验室检查[如外周血淋巴细胞绝对值计数、血红蛋白、血小板、β2-微球蛋白(β2-microglobulin,β2-MG)、乳酸脱氢酶(lactate dehydrogenase,LDH)水平]的相关性。结果:(1)CLL患者FISH检测至少具有1种分子遗传学异常者为56例,发生率为75.68%。(2)各种遗传学异常情况与患者性别、年龄无相关性(P>0.05),与外周血淋巴细胞绝对值计数、血红蛋白、血小板、β2-MG、LDH的表达水平无明显相关性(P>0.05)。(3)就Binet分期而言,12号染色体三体(+12)仅在B期和C期患者中检出,在Binet分期中的分布差异具有统计学意义(χ^(2)=4.696,P=0.041);C期的生存时间明显短于A和B期(χ^(2)=14.242,P=0.001)。就改良的Rai分期而言,ATM基因缺失仅在高危组检出,且此种分布差异具有统计学意义(χ^(2)=5.40,P<0.001);低中危组的生存时间明显优于高危组(χ^(2)=12.393,P<0.001);单纯del(13q)核型异常的CLL患者生存时间明显长于伴有其他核型异常及复杂核型的患者(χ^(2)=8.138,P=0.017)。结论:CLL为惰性疾病,但其疾病进展和临床预后具有高度异质性。FISH检测结果联合疾病临床分期可更好地预测患者预后。

Objective:This study aims to investigate the correlation between cytogenetic detected by fluorescence in situ hybridization(FISH)and the patients’clinical features in chronic lymphocytic leukemia(CLL),to analyze the prognostic value.Methods:Total 74 cases of chronic lymphocytic leukemia patients were collected in Nantong University Affiliated Hospital from June2013 to October 2020,with 74 cases of newly diagnosed patients,43 males and 31 females.The clinical characteristics of patients,laboratory tests,bone marrow smear results,immunological typing results,FISH results and other information were collected.The correlation between cytogenetic abnormalities and gender,age,the clinical Binet staging,Rai staging and the related laboratory examinations[including peripheral blood lymphocyte absolute count,hemoglobin,platelets,lactate dehydrogenase(LDH),β2-microglobulin(β2-MG)]were analyzed.Results:(1)Cytogenetic abnormalities were found in 56 of 74 CLL patients(75.68%).(2)There was no significant relationship among the cytogenetic abnormalities and the sex,age,peripheral blood lymphocytes,hemoglobin,platelet,β2-MG,LDH expression level(P>0.05).(3)In the case of Binet stage,chromosome 12(+12)was only detected in stage B and stage C,and the differences were statistically significant(χ^(2)=4.696,P=0.041).The survival time of group C was significantly shorter than that of group A and group B(χ^(2)=14.242,P=0.001).In the modified Rai stage,the deletion of ATM gene were only detected in the high risk group,and this distribution had statistical differences(χ^(2)=5.40,P<0.001).The survival time of the high risk group was shorter than that in the low and medium risk group(χ^(2)=12.393,P<0.001).The survival time of CLL patients with simple del(13 q)karyotype abnormality was significantly longer than that of patients with complex karyotype(χ^(2)=8.138,P=0.017).Conclusion:CLL is an inert disease,but its disease progression and clinical prognosis are highly heterogeneous.FISH test results combined with disease clinical staging can better predict the prognosis.