FLT3-ITD、NPM1和C-KIT基因突变在成人急性髓系白血病中的表达及临床意义

Expression of FLT3-ITD、NPM1 and C-kit Gene Mutation in Adult Acute Myeloid Leukemia and The Clinical Significance

目的探讨成人急性髓系白血病患者中FLT3-ITD、NPM1、C-kit基因突变表达及临床意义。方法采用PCR技术检测50例成人急性髓系白血病患者治疗前后FLT3-ITD、NPM1、C-kit表达,比较分析FLT3-ITD、NPM1、C-kit突变与临床资料、细胞遗传学的关系及预后影响。结果 50例急性髓系白血病中NPM1突变检出率占38%,在正常核型占61.9%,显著高于在异常核型(P<0.05);FLT3-ITD突变检出率32%,正常核型占38.1%,与在异常核型相比无显著性差异(P>0.05);C-kit突变检出率10%,核型为t(8;21)占80%。FLT3-ITD、NPM1突变初诊时WBC、LDH、α-HBDH显著高于无突变患者(P<0.05);在NPM1突变患者中伴FLT3-ITD突变占68.42%,显著高于在无NPM1突变患者中伴FLT3-ITD突变占的9.68%(P<0.05);单纯NPM1突变CR率100%,显著高于无三基因突变的患者54.16%(P<0.05),FLT3-ITD、NPM1突变CR率46.15%,显著低于单纯NPM1突变CR率100%(P<0.05)。CR的患者FLT3-ITD、NPM1、C-kit突变均转阴,复发患者再次检出突变早于骨髓复发。结论 FLT3-ITD、NPM1及C-kit基因突变在急性髓系白血病上有特殊的分布,并且与白细胞数、骨髓原始细胞比例、血小板数、LDH、α-HBDH密切相关,三基因突变可作为判断预后及监测微小残留病灶的指标。

Objective To investigate and discuss the expression and clinical significance of FLT3-ITD ,NPMI ,C-kit in adult patients with acute myeloid leukemia. Methods The expression of FLT3-ITD, NPM1, C-kit were detected before and after treat- ment by PCR in 50 cases of adult patients with AML. Technology and comparated analye is the ralutionship of FLT3-ITD NPM1 C-kit mutation with clinical data, cytogenetics and prognosos. Results In 50 cases of AML NPM] mutation positie is 38%, the nor- mal karyotype group was significantly higher than abnormal karyotype （61.9%vs38% P 〈 0.05） ; FLT3-1TD mutation positie rate is 32%. There was no statistial diffenence between normal karyotype and abnormal karyotype （38.1%vs27.27% P 〉 0.05）; C-kit muta- tion positie rate is 10%, among these patienis 80% was detected. WBC ,LDH, -HBDH was significantly higher in newly diaynosed pa- tients with FLT3-ITD and NPM1 mutation than that without the mutation（P 〈 0.05）. In NPM1 mutation positie pationts FLT3-ITD mutation positie rate was much higer than NPM1 negatie FLT3-ITD positie rate （68.42%vs9.68% P 〈 0.05） ;The CR rate of Simple NPM1 mutation was higher than these three gene negatie and both NPM1 and FLT3-ITD positie （100% vs54.16% P〈0.05）, FLT3-ITD, NPM1,C-kit mutations positie patients who got CR turned to negatie. It is early bone marrow relapse that the time that mutation detected again was earlier than bone marrow relapse in patient. Conclusion There is special distribution of FLT3-ITD NPM1 C-kit gene mutation in AML patients. And closely related to the WBC number, PLT number, percentage of bone marrowblasts, LDH-HBDH. FLT3-1TD NPMI C-kit gene mutation can be the index to assess and monitor minimal residual disease.