急性非淋巴细胞白血病患者骨髓中LKB1基因的表达水平及临床意义

Expression of LKB1 gene in bone marrow of patients with acute non-lymphocytic leukemia and its clinical significance

目的探讨人类肝激酶B1 (Liver kinase B1,LKB1)基因在急性非淋巴细胞白血病(AML)患者骨髓中表达水平,及其与患者预后的相关性。方法选取2015年5月~2017年1月本院收治的90例AML患者标本为研究对象,同时选取非恶性血液系统疾病患者骨髓标本30例为对照组。采用实时荧光定量PCR法(qRT-PCR)检测各组骨髓中LKB1基因表达水平。Western Blot检测LKB1蛋白表达。Kaplan-Meier生存分析LKB1基因与AML预后的相关性。结果 AML患者骨髓中LKB1基因突变率、mRNA及LKB1蛋白表达量明显低于对照组(χ^(2)=13.274,t=34.134,P<0.05)。LKB1基因扩增率、mRNA表达量从高到低顺序M1(81%,17/21)>M5(78.6%,11/14)>M6(75%,3/4)>M2(42.4%,14/33)>M4(41.7%,5/12)>M3(35.3%,6/17)。LKB1高扩增组AML患者的随访生存率高于LKB1低扩增患者(χ^(2)=8.039,P<0.05)。LKB1高扩增组的中位生存时间高于LKB1低扩增组(27.3个月vs 19.8个月)(x^(2)=5.552,P<0.05)。LKB1高扩增组患者的化疗后感染、化疗后复率及髓外浸润发生率低于LKB1低扩增患者,差异无统计学意义(P>0.05)。结论 AML患者骨髓中LKB1基因低扩增,且表达水平越低AML病情越严重,预后越差。

Objective To investigate the expression level of liver kinase B1(LKB1)gene in bone marrow of patients with acute non-lymphoblastic leukemia(AML)and its correlation with prognosis.Methods A total of 90 AML patients from May 2015 to January 2017 were selected as study subjects,and 30 cases of bone marrow specimens from non-malignant hematologic diseases were selected as control group.The expression of LKB1 mRNA in bone marrow was detected by real-time fluorescent quantitative PCR(qRT-PCR).The expression of LKB1 protein was detected by Western blot.The correlation between LKB1 mRNA and prognosis of AML was analyzed by Kaplan-Meier survival analysis.Results The mutation rate of LKB1 gene,the mRNA and LKB1 protein expression in bone marrow of AML patients was lower than those of control group(χ^(2)=13.274,t=34.134,t=45.235,P<0.05).The mutation rate of LKB1 gene and the mRNA expression from high to low order is M1(81%,17/21)>M5(78.6%,11/14)>M6(75%,3/4)>M2(42.4%,14/33)>M4(41.7%,5/12)>M3(35.3%,6/17).Thefollow-up survival rate of patients with AML in the LKB1 high amplification group was higher than that of patients with LKB1 low amplification(χ2=8.039,P<0.05)The median survival time of the LKB1 high amplification group was higher than that of the LKB1 low amplification group(27.3 months vs 19.8 months)(χ^(2)=5.552,P<0.05).The incidence of post-chemotherapy infection,post-chemotherapy recurrence and extramedullary infiltration in the LKB1 high amplification group was lower than that in patients with LKB1 low amplification(P>0.05).Conclusion The expression level of LKB1 gene in patients with AML is low,moreover the more low expression level of LKB1 gene were,the more severe ill condition and more poor prognosis.