CAJ | 학술논문

目的探讨急性髓系白血病(AML)患者异柠檬酸脱氢酶(IDH)1及IDH2基因突变的发生率,并探讨其临床特征及意义.方法选取2005年2月至2011年3月经MICM分型确诊的570例初治AML患者,采用骨髓单个核细胞基因组DNA,PCR方法扩增IDH1、IDH2基因4号外显子,基因测序检测IDHl R132及IDH2 RI40/R172基因突变,分析患者临床特征并判定其疗效.结果 570例AML患者中90例检测到IDH基因突变,突变率为15.79％,其中IDH1突变27例(4.74％),IDH2突变63例(ll.05％).未发现有患者同时获得IDH1和IDH2突变.IDH突变与FAB分型中AML-M1显著相关(P＜0.01)；突变组年龄、初诊外周血血小板计数与未突变组比较,差异有统计学意义(中位数:53岁比40岁,52×109/L比31×109/L,均P＜0.01)；IDH基因突变与正常核型、NPM1基因突变,尤其是NPM1基因突变未伴FLT3-ITD基因突变的基因型相关,但与WT1、FLT3-TKD及MLL-PTD突变无明显的相关性.在非M3型患者中,突变组的化疗完全缓解率低于未突变组(58.1％比77.9％),差异有统计学意义(P＜0.05).在不伴NPM1基因突变的患者或在正常核型的亚群中,IDH基因突变者预计2年总生存率低于该基因未突变者(28.4％比51.3％,P＜0.01).结论 IDH基因突变更易存在于年龄偏大的AML患者中,IDH突变与临床特点、疗效具有一定相关性,提示是预后不良的分子学标志.
목적 탐토급성수계백혈병(AML)환자이저몽산탈경매(IDH)1급IDH2기인돌변적발생솔,병탐토기림상특정급의의.방법 선취2005년2월지2011년3월경MICM분형학진적570례초치AML환자,채용골수단개핵세포기인조DNA,PCR방법확증IDH1、IDH2기인4호외현자,기인측서검측IDHl R132급IDH2 RI40/R172기인돌변,분석환자림상특정병판정기료효.결과 570례AML환자중90례검측도IDH기인돌변,돌변솔위15.79％,기중IDH1돌변27례(4.74％),IDH2돌변63례(ll.05％).미발현유환자동시획득IDH1화IDH2돌변.IDH돌변여FAB분형중AML-M1현저상관(P＜0.01)；돌변조년령、초진외주혈혈소판계수여미돌변조비교,차이유통계학의의(중위수:53세비40세,52×109/L비31×109/L,균P＜0.01)；IDH기인돌변여정상핵형、NPM1기인돌변,우기시NPM1기인돌변미반FLT3-ITD기인돌변적기인형상관,단여WT1、FLT3-TKD급MLL-PTD돌변무명현적상관성.재비M3형환자중,돌변조적화료완전완해솔저우미돌변조(58.1％비77.9％),차이유통계학의의(P＜0.05).재불반NPM1기인돌변적환자혹재정상핵형적아군중,IDH기인돌변자예계2년총생존솔저우해기인미돌변자(28.4％비51.3％,P＜0.01).결론 IDH기인돌변경역존재우년령편대적AML환자중,IDH돌변여림상특점、료효구유일정상관성,제시시예후불량적분자학표지.
Objective To explore the prevalence and clinical characteristics of isocitrate dehydrogenase (IDH)1 R132 and IDH2 R140/R172 gene mutations in acute myeloid leukemia (AML) patients.Methods Polymerase chain reaction (PCR) and direct sequencing were used to sequence exon 4 of IDH gene in 570 AML patients from 2005 to 2011.Results In a cohort of 570 patients,AML IDH gene mutation was found in 90 (15.79％) patients.IDH1 and IDH2 mutations were detected in 27 (4.74％) patients and 63 (11.05％) patients respectively.None of them had the combined mutations of IDH1 and IDH2.The highest frequency of IDH mutations was found in AML M1 (according to the FAB scheme) compared with all other subtypes (P ＜ 0.01).The median age was 53 years in mutated group versus 40 years in wild-type group (P =0.010).Mutated and wild-type groups had no significant difference in gender,white blood cell count at diagnosis,hemoglobin count and bone marrow blast percentage,excepting for blood platelets level (median 52 × 109/L vs 31 × 109/L,P ＜ 0.01).IDH gene mutations were associated with cytogenetically normal (CN)-AML,NPM1 mutations and particularly with the genotype of mutated NPM1 without FLT3-ITD.IDH gene mutations had no significant correlation with WT1,FLT3-TKD and MLL-PTD mutations.IDH mutated patients had a lower complete remission rate than unmutated in non-M3 patients (58.1％ vs 77.9％,P ＜0.05).And the patients with mutant IDH gene were associated with a shorter overall survival(28.4％ vs 51.3％,P ＜ 0.01).Conclusion IDH gene mutations are more prevalent in elder AML patients and it may constitute a molecular marker for a poor prognosis in AML.