| Objective:To investigate the correlation between common gene mutations and clinical features of acute myeloid leukemia and its impact on prognosisMethods:From January 2015 to August 2017,the clinical data of 233 new patients with acute myeloid leukemia(non-M3)who were hospitalized in the Department of Hematology,Shihezi University Medical College and the Department of Hematology,People’s Hospital of Xinjiang Uygur Autonomous Region were collected.Clinical data such as gender,age,and,ethnicity white blood cell count(WBC),hemoglobin content(HB),platelet count(PLT),karyotype,FAB classification,gene mutation,etc.,and followed up.The correlation between gene of mutations and clinical features and the impact on prognosis were retrospectively analyzed.Results:1.Frequency and distribution of gene mutations:There were as followed,NPM1 18.5%(43/233),FLT3-ITD 18.0%(42/233),CEBPA 16.7%(39/233),DNMT3A 14.4%(14/97),IDH210.0%(9/90),TP53 9.7%(3/31),NRAS 9.7%(3/31),TET2 8.9%(8/90),PHF6 6.9%(6/87),RUNX1 6.5%(2/31),IDH1 4.4%(4/90),MLL 3.5%(3/86),ASXL1 3.4%(3/89),C-KIT 3.4%(8/233),WT1 3.2(1/31).The mutational profiles of Han,Uygur and Kazak genes were statistically different(Han vs.Uygur 0.020,Han vs Kazakh 0.000,Uygur vs Kazakh 0.000,P=0.020,0.000,0.000,respectively).2.Correlation between clinical features and gene mutations:(1)There was a significant difference in the distribution of gene mutations between the age≤67 year group and the age≥67year group(P=0.000).(2)Statistical analysis of FLT3-ITD,NPM1,CEBAP,and DNMT3A with a mutation frequency above 10.0%showed that they were unevenly distributed between different FAB subtypes,and there was a statistically significant difference(χ~2=192.621,P=0.000),in the prognosis group,FLT3-ITD mutations were mainly seen in the intermediate-risk group and the high-risk group.There were no mutations in the low-risk group,and the differences between the groups were statistically significant(P=0.002),NPM1,CEBPA,DNMT3A mutations.There was no statistical difference between the three groups.(3)According to the WBC group,the FLT3-ITD and DNMT3A mutations were more common in the WBC>47.9×109/L group,and the difference was statistically significant(P=0.000 and0.022,respectively).According to the PLT group,CEBPA single mutations mostly appeared in the PLT>94×109/L group,while the CEBPA double mutations appeared in the PLT≤94×109/L group(P=0.001).(4)The detected genes did not show statistical differences in gender distribution and HB grouping.3.The prognostic factors of the intermediate-risk group:The univariate survival analysis showed that the median overall survival(OS)of the age≤67 year group and age>67 year group were 19.00 months and 8.60 months,respectively,and the difference was statistically significant(HR=0.277,P=0.000);The median OS of WBC≤47.9×109/L group and WBC>47.9×109/L group were 20.1 months and 9.7 months,respectively,and the difference was statistically significant(HR=0.399,P=0.000).The median survival time of HB≤67.0g/L group and HB>67.0g/L group were 11.00 months and 20.10 months,respectively,the difference was statistically significant(HR=2.18,P=0.003);PLT>94.0×109/L group The median survival time with PLT≤94.0×109/L group was 23.87 months and 15.23 months,respectively,and the difference was statistically significant(HR=0.586,P=0.034).Compared with the FLT3-ITD wild group,the overall survival time was significantly shortened in the FLT3-ITD mutation group.The median survival time was 10.20 months and 20.10 months,respectively.The difference was statistically significant(HR=2.698,P<0.001).Compared with CEBPA-negative group,the total survival time of CEBPA double mutation group was prolonged,the difference was statistically significant(HR=0.307,P=0.016).There was no statistical difference in total survival time between CEBPA single mutation group and CEBPA negative group(HR=0.733,P=0.319).Multivariate analysis showed that FLT3-ITD mutation,age greater than 67 years,and initial white blood cell count greater than 47.9×109/L were independent prognostic risk factors(HR=4.272,6.011 and 1.689,respectively;P=0.000,0.000 and 0.046,respectively).The CEBPA double mutation and PLT>94.0×109/L were favorable prognostic factors(HR=0.321 and 0.531,respectively,and P=0.015 and 0.040,respectively).The OS of FLT3-ITD-/NPM1+group was significantly higher than that of FLT3-ITD+/NPM1-group.The median OS was 27.80 months and 9.70 months,respectively.The difference was statistically significant(HR=0.209,P=0.002);FLT3-ITD+/NPM1+The median OS of the group and the FLT3-ITD+/NPM1-group were 27.80 months and 9.70 months,respectively,and the difference was not statistically significant(HR=0.933,P=0.834).Conclusions:1.AML gene mutations are associated with age,FAB classification,white blood cell count,and platelet count.2.FLT3-ITD mutation,age greater than 67 years,white blood cell count greater than47.9×10~9/L is an independent risk factor for the prognosis of AML in the intermediate-risk group;CEBPA double mutation,platelet count greater than 94.0×10~9/L is a prognostic factor.3.NPM1,DNMT3A and accompanying gene mutations affect the prognosis of AML in the intermediate-risk group.4.There are differences in the mutational profiles of AML genes in different ethnic groups.These will be subject to forthcoming research. |
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