伴异柠檬酸脱氢酶1基因突变急性髓系白血病的临床特征及预后

Clinical characteristics and prognostic analysis in acute myeloid leukemia with isocitrate dehydrogenase 1 gene mutation

目的评估异柠檬酸脱氢酶1(IDH1)基因突变在急性髓系白血病(AML)患者中的发生率、临床特征及预后意义。方法选取2015年1月至2018年9月于我院初诊的220例AML患者,应用PCR方法扩增IDH1基因的4号外显子,通过基因测序检测IDHl基因突变情况,分析IDH1突变患者的临床特征及预后意义。结果220例AML患者中检出IDH1基因突变者9例,突变率为4.09%,均为R132H突变。突变组患者中位年龄为50岁,未突变患者中位年龄为43岁,两组间比较有差异,P<0.05;突变组患者初诊血小板计数为68(48~175)×10^(9)/L,未突变组患者初诊血小板计数为43(10~253)×10^(9)/L,两组间比较有差异,P<0.05。IDH1基因突变均发生在AML-M5和AML-M4中,未见其他亚型。正常核型组IDH1基因突变率6.48%(7/108),高于异常核型组IDH1基因突变率1.43%(1/70),无统计学差异。IDH1基因突变与NPM1基因突变有相关性,P<0.05,与FLT3-ITD基因突变无明显相关性。IDH1基因突变患者免疫表型易出现CD34-、CD33+、CD64+(P均<0.05)。IDH1突变组化疗完全缓解率为50%(4/8),低于非突变组化疗完全缓解率80.92%(140/173),P<0.05。所有随访患者中,IDH1突变组2年总生存率为25%(1/4),低于非突变组2年总生存率67.32%(103/153),P<0.05;正常核型患者中,IDH1突变组2年总生存率为28.57%(2/7),低于非突变组2年总生存率65.91%(58/88),P<0.05;不伴有NPM1突变的患者中,IDH1突变组2年总生存率为0%,明显低于非突变组2年总生存率67.20%(84/125),P<0.05;伴有NPM1突变的患者中,IDH1突变组2年总生存率为40%(2/5),非突变组2年总生存率为67.86%(19/28),差异无统计学意义。结论IDH1基因突变患者年龄较大,血小板计数较高。IDH1基因突变易发生于正常核型患者,易见于AML-M5和AML-M4。IDH1基因突变与NPM1基因突变有相关性。IDH1基因突变对AML患者的预后有不良影响,是预后不良的分子标志,伴有NPM1突变时,对患者的预后无明显影响。

Objective To assess the frequencies and clinical characteristics and prognostic significance of the isocitrate dehydrogenase 1(IDH1)mutations in acute myeloid leukemia(AML).Methods Two hundred and twenty patients with AML newly diagnosed in our hospital from January 2015 to September 2018 were selected.PCR was used to amplify the exon 4 of IDH1 gene,gene sequencing was used to detect the mutation of IDHL gene,and the clinical characteristics and prognostic significance of patients with IDH1 mutation were analyzed.Results IDH1 gene mutation was detected in 9 of 220 AML patients,and the mutation rate was 4.09%,all of which were R132H mutation.The median age was 50 years in the mutation group and 43 years old in the non-mutation group,and there was a difference between the two groups,P<0.05.Blood platelets median level was 68×10^(9)/L in the mutated group and 43×10^(9)/L in the non-mutation group,and there was a difference between the two groups,P<0.05.IDH1 gene mutations all occurred in AML-M4/M5,and they were not observed in other AML subtypes.The rate of IDH1mutations was 6.48%in AML with normal karyotype,higher than 1.43%in AML with abnormal karyotype,without signifi cant differences.IDH1 gene mutations were associated with NPM1mutations,P<0.05,but not associated with FLT3-ITD muta-tions.Patients with IDH1 mutations were prone to CD34-、CD33+、CD64+(averge P<0.05).IDH1 mutated patients had a lower complete remission rate than unmutated patients(50%vs 80.92%),P<0.05.In all follow-up patients,the 2-year over all survival rate in IDH1 mutation group was lower than in the non-mutation group(25%vs 67.32%),P<0.05.In the patients with normal karyotype,the 2 years overall survival rate in the IDH1 mutation group was lower than in the non-mutation group(28.57%vs 65.91%),P<0.05.In the patients without mutated NPM1,the same result was obtain(0%vs 67.20%),P<0.05.In the patients with mutated NPM1,the 2 years overall survival rate was 40%in the IDH1 mutation group and 67.86%in the non-mutation group,without statistical differences.Conclusion IDH1 gene mutations are more common in AML patients with older age,higher platelets level.IDH1 gene mutations are associated with normal karyotype,AML-M5/M4 and NPMl gene mutations.IDH1 gene mutation was correlated with NPM1 gene mutation.IDH1 gene mutation has an adverse effect on the prognosis of AML patients and is a molecular marker of poor prognosis.In the patients with mutated NPM1,IDH1 gene mutations have no effect on prognosis.