摘要
目的探讨急性髓细胞白血病（acute myeloid leukemia，AML）患者的基因突变情况及临床特征。方法应用PCR扩增产物直接测序法检测412例初诊AML患者FLT3-ITD、NPMl、CEBPA、c-KIT、DNMT3A和ND4等基因的突变情况，同时分析其染色体核型，分析不同的基因及染色体突变患者的预后。结果在412例患者中，FLT3-ITD，NPM1、CEBPA、c-KIT、DNMT3A和ND4基因的突变率分别为9．0％（26／289）、19．1％（50／262）、18．9％（34／180）、3．4％（7／208）、6．6％（9／137）和6．9％（4／58）。基因突变预后不良组的患者血小板计数低于预后中等和良好的患者（P=0．001和P=0．001）。基因突变预后不良、中等和良好的患者的总生存均未达到中位数，且差异无统计学意义（P〉0．05）。在完全缓解率方面，基因突变预后各组之间的差异均无统计学意义（P〉0．05）。基于染色体核型分组，细胞遗传学预后中等的患者白细胞计数分别高于预后良好和预后不良的患者（P〈0．001和P=0．004），预后中等的患者血小板计数高于预后良好的患者（P=0．018），而血红蛋白在各组之间的差异无统计学意义（P〉0．05）。细胞遗传学预后不良患者的总生存与预后良好及中等的患者相比更短，差异有统计学意义（P〈0．001和P=0．003），预后良好组的完全缓解率高于细胞遗传学预后中等组（P=0．001）。在细胞遗传学预后中等的患者中，基因突变预后不良、中等和良好患者的白细胞及血小板计数、血红蛋白、完全缓解率和总生存的差异均无统计学意义（P〉0．05）。结论对于AML患者而言，基因突变与细胞遗传学分析的结果可互为补充，有助于使患者预后的更加精细化和个体化。
Objective To correlate the （AML） with mutations of FLT3-ITD, NPM1, clinical features of patients with acute myeloid leukemia CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations. Methods Somatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients. Results The mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 were 9.0% （26/ 289）, 19. 1% （50/262）, 18. 9% （34/180）, 3. 4%（7/208）, 6. 6% （9/137） and 6. 9% （4/58）, respectively. Patients with poor prognosis based on genetic mutations had lower blood platelet count than those with intermediate and good prognosis （P= 0. 001 and P = 0. 001, respectively）. None of the three groups attained median overall survival （OS） （P〉0.05）. The complete remission （CR） was similar among the three groups （P〉 0. 05）. For patients with different prognosis based on cytogenetic findings, white blood cell count in those with intermediate prognosis was higher than those with good and poor prognosis （P〈0. 001 and P=0. 004, respectively）, while the blood platelet count of the intermediate group was higher than that of the group with good prognosis （P= 0. 018）. No significant difference was found among the three groups in terms of hemoglobin level （P〉0.05）. The group with poor prognosis has attained shorter OS compared with those with good and intermediate prognosis （P〈0. 001 and P= 0. 003, respectively）. However, the CR rate of the group with good prognosis was higher than that of the intermediate group （P= 0. 001）. For the group with intermediate prognosis, presence of genetic mutations did not correlate with the clinic characteristics such as white blood cell count, blood platelet count, hemoglobin level, OS and CR rate （P〉0. 05 for all comparisons）. Conclusion Genetic mutations combined with cytogenetic analysis can facilitate the prognosis and personalized treatment for patients with AML.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2017年第6期806-811,共6页
Chinese Journal of Medical Genetics
作者简介
通信作者：乔纯，Email：qiaochun001004@163．com
