老年急性非早幼粒细胞白血病NPM1及FLT3-ITD基因突变特征及临床意义

目的:探讨老年急性非早幼粒细胞白血病（non-acute promyelocytic leukemia,non-APL）NPM1及FLT3-ITD基因突变特征及临床意义。方法:回顾性分析本院2011年1月至2018年6月接受NPM1、FLT3-ITD基因突变检测的98例老年non-APL患者临床资料,统计NPM1、FLT3-ITD基因突变阳性率,分析不同核型non-APL患者NPM1、FLT3-ITD基因突变情况,并比较 NPM1/FLT3-ITD基因突变阳性与阴性患者性别、年龄、白细胞、血小板、血红蛋白、骨髓原始细胞、CD34+、CD117+的关系。结果:NPM1基因突变阳性20例,占20.41%;FLT3-ITD基因突变阳性15例,占15.31%;NPM1、FLT3-ITD基因突变双阳性5例,占5.10%。正常核型38例,占38.78%,正常核型患者NPM1、FLT3-ITD基因突变阳性率及双阳性率均显著高于异常核型者（P<0.05）。NPM1基因突变阳性患者白细胞计数、血小板计数均显著大于NPM1基因突变阴性者,CD34+比例显著小于NPM1基因突变阴性者（P<0.05）;FLT3-ITD基因突变阳性患者白细胞、骨髓原始细胞均显著大于FLT3-ITD基因突变阴性者（P<0.05）。NPM1基因突变阳性患者1疗程CR率、总CR率均显著高于NPM1基因突变阴性者（P<0.05）;FLT3-ITD基因突变阳性患者1疗程CR率、总CR率均显著低于FLT3-ITD基因突变阴性者（P<0.05）。结论:对老年non-APL患者行FLT3-ITD及NPM1基因突变检测,可指导临床治疗及疗效评估。     

DNMT3A、FLT3-ITD合并NPM1基因突变正常核型急性髓系白血病患者的临床特征及预后分析

目的 分析DNMT3A、FLT3-ITD合并NPM1基因突变的正常核型急性髓系白血病(AML)患者的临床特征,探讨该类患者的预后.方法 回顾性分析2005年12月至2014年6月就诊的109例正常核型AML患者的临床特征及预后.其中DNMT3A/FLT3-ITD/NPM1+AML患者共25例,单独FLT3-ITD+ AML患者共32例,单独NPM1+AML患者24例,单独DNMT3A+ AML患者28例.结果 25例DNMT3A/FLT3-ITD/NPM1+ AML患者平均年龄46岁,伴有高白细胞(81.7×109/L)及较高的骨髓原始细胞(66.3％).其中,17例选择大剂量化疗,8例行异基因造血干细胞移植,与DNMT3A+、FLT3-ITD+、NPM1+AML组比较,差异均无统计学意义.25例DNMT3A/FLT3-ITD/NPM1+患者的3年总生存率为17.65％,3年无病生存率为13.88％,与DNMT3A+、FLT3-ITD+、NPM1+AML组差异均有统计学意义(P值分别为0.049 9、0.036 1、0.013 4),3年无病生存率差异无统计学意义(均P＞ 0.05).结论 DNMT3A、FLT3-ITD合并NPM1基因突变的正常AML患者往往合并高的外周血白细胞及骨髓原始细胞,预后较差.     

急性髓细胞白血病NPM1和FLT3-ITD突变检测临床意义分析

目的:研究核仁磷酸蛋白1(NPM1)FMS样酪氨酸激酶3(FLT3)基因内部串联重复(ITD)突变在急性髓细胞白血病(AML)中发生的情况,并了解其临床特征及预后意义.方法:分别应用高分辨熔解曲线(HRM)和变性高效液相色谱技术(DHPLC)检测103例初诊AML患者NPM1和FLT3-ITD突变情况,并结合临床资料进行分析.结果:103例初诊AML患者中,31例发现NPM1基因突变,20例发现FLT3-ITD突变,阳性率分别为30.1％和19.4％,而在核型正常组中所占的比例分别为47.6％(20/42)和26.2％(11/42).FLT3-ITD突变型外周血白细胞计数高,t=2.21,P=0.037;骨髓原始细胞比例高,t=2.44,P=0.023;NPM1突变型亦表现为高外周血白细胞计数,t=2.24,P=0.034.在非M3患者中,NPM1突变型的CR与野生型差异无统计学意义,但第1次化疗的CR(76.9％)明显高于野生型患者(35.0％),x2=12.78,P=0.000 35;FLT3-ITD突变型患者的CR为58.8％,野生型患者为82.6％,两者比较,x2=4.48,P=0.034;FLT3-ITD突变型患者第1次化疗的CR为17.6％,而野生型患者为55.1％,两者比较,x2=6.23,P=0.012.31例NPM1基因突变中有6例合并FLT3-ITD突变,NPM1+/FLT3-ITD-组的CR最高(85.0％),1年内RR率最低(17.6％);NPM1-/FLT3-ITD+组的CR最低(54.5％),1年内RR率最高(50.0％).结论:NPM1和FLT3-ITD突变是AML患者常见的分子遗传学异常,与预后密切相关,可成为目前细胞遗传学预后分组的重要补充,对于指导AML患者的个体化治疗具有重要的临床价值.     

老年急性髓细胞白血病患者FLT3-ITD基因突变的临床意义

 目的　分析老年急性髓细胞白血病（AML）Fms样酪氨酸激酶3内部串联重复序列（FLT3-ITD）基因突变及其临床意义。方法　采用聚合酶链反应-变性高效液相色谱技术（PCR-DHPLC）分析30例初发老年AML患者骨髓单个核细胞FLT3-ITD突变。结果　30例老年AML患者FLT3-ITD突变阳性率26.67 %（8／30）,对照组均未检测到该突变;FAB各亚型FLT3-ITD突变率不同,有M3型突变率较高的趋势;所检测到FLT3-ITD突变均为杂合突变,突变均在阅读框内;不同预后核型组FLT3-ITD突变阳性率不同,预后中等核型组突变率较高,达40.0 %（6／15）;显示FLT3-ITD突变阳性者具有高白细胞、白血病细胞、完全缓解（CR）率低等临床特点。结论　FLT3-ITD突变阳性老年AML患者预后差,且多发生于预后中等核型组;FLT3-ITD突变检测在一定程度上可以弥补细胞遗传学的不足,有可能成为老年AML患者常规检测项目,以指导治疗判断预后。     

FLT3基因突变在急性早幼粒细胞白血病中的表达及临床意义

目的:检测急性早幼粒细胞白血病（acute promyelocytic leukemia,APL）患者FMS样酪氨酸激酶3（FLT3）基因内部串联重复（ITD）突变和酪氨酸激酶结构域（TKD）突变的表达,并探讨临床意义。方法:提取APL患者骨髓单个核细胞DNA,采用聚合酶链反应及测序技术检测FLT3-ITD和FLT3-TKD,分析临床资料及预后。结果:在77例APL患者中,23例（29.9%）检出 FLT3-ITD,7例（9.1%）检出FLT3-TKD点突变,具体包括5例D835Y、1例N841I、1例D835Y和D835H复合杂合子。FLT3-ITD与高白细胞计数相关（P=0.033）,而FLT3-TKD并无此相关性。与无FLT3基因突变患者相比,尽管FLT3-ITD和TKD突变患者的完全缓解率（CR）、总生存期（OS）、无事件生存期（EFS）均相对更差,除FLT3-TKD与缩短EFS显著相关（P=0.043）外,差异均无统计学意义。值得注意的是,无论是FLT3-ITD（P=0.011）还是FLT3-TKD（P= 0.034）均提示高复发风险。多因素分析表明FLT3-ITD（HR=6.381,P=0.037）、FLT3-TKD（HR=5.198,P=0.009）、骨髓早幼粒细胞比例（HR=1.174,P=0.020）、高白细胞计数（WBC>10×109/L）（HR=9.067,P=0.011)可作为独立预后因素提示高复发风险。结论:FLT3-ITD和TKD在APL中均有表达,FLT3-ITD患者的白细胞计数高。虽然FLT3基因突变对APL患者的CR率和OS无显著影响,但可作为一个有价值的指标用于评估复发风险。     

化学法提取贮存骨髓涂片DNA检测Fms样酪氨酸激酶3基因突变预测急性髓系白血病患者预后

目的 探讨用化学法(苯酚:氯仿:异戊醇法)从贮存的骨髓涂片中提取微量DNA检测Fms样酪氨酸激酶3内部串联重复(FLT3-ITD)突变情况,分析其对急性髓系白血病(AML)预后的预测价值.方法 采用化学法从58例-20℃贮存1~5年的骨髓涂片(AML 48例和非恶性血液病10例)中提取微量DNA,采用聚合酶链反应(PCR)技术检测患者FLT3-ITD突变情况.结果 48例初治AML患者中6例(12.5%)检测到FLT3-ITD,10例非恶性血液病患者中均未检测到FLT3-ITD.FLT3-ITD阳性AML患者初次诱导完全缓解(CR)率较FLT3-ITD阴性者低[0(0/6)比77.78%(21/27),P=0.001],总生存时间短(x2=7.274,P=0.007).肝、脾大和FLT3突变是影响AML患者初次化疗CR的危险因素(OR=7.2,P=0.12;OR=36.3,P=0.10).FLT3-ITD是初治AML患者不良预后的危险因素(RR=9.088,P=0.029).结论 使用化学法提取贮存的AML患者骨髓涂片微量DNA可在临床中应用,是进行回顾性分子生物学研究的重要实验方法.从骨髓涂片中提取微量DNA检测FLT3-ITD可用于预测AML预后.     

急性髓系白血病患者骨髓杯状核细胞阳性与FMS样酪氨酸激酶3基因内部串联重复突变相关性的Meta分析

 【摘要】　目的　评价急性髓系白血病（AML）患者骨髓杯状核细胞阳性与FMS样酪氨酸激酶3基因内部串联重复（FLT3-ITD）突变的相关性。方法　检索国内外各类大型数据库中2000年至2011年发表的有关AML患者杯状核细胞阳性与发生FLT3-ITD突变关系的文献,采用Meta分析方法,利用Statal 1软件评价杯状核细胞阳性与FLT3-ITD突变之间的关系。计算OR值及其95 % CI,Begg检验法和Egger检验法评价发表性偏倚。结果　共纳入4篇文献,包括225例患者,其中杯状核细胞阳性的AML患者76例,杯状核阴性的AML患者149例（所有研究的AML患者均除外AML-M3、M5型）。对总体人群进行Meta 分析,发现骨髓杯状核细胞阳性与FLT3-ITD突变的发生密切相关（OR＝2.59,95 % CI 1.55～4.33,P＝0.00）。结论　AML患者杯状核阳性与FLT3-ITD突变相关,该形态学特点可以指导临床医生合理选择检测项目。杯状核细胞阳性的患者也许可以成为AML的一种新亚型。     

核心结合因子相关性急性髓系白血病常见基因突变和细胞遗传学分析

目的：研究核心结合因子相关性急性髓系白血病（CBF-AML）c-Kit、FLT3基因突变发生情况及患者的核型特征。方法采用基因组 DNA 聚合酶链反应（PCR）法结合碱基测序方法,检测48例CBF-AML 患者初诊时 c-Kit、FLT3基因内部串联重复（ITD）突变和 FLT3第二酪氨酸激酶结构域（TKD）点突变发生情况及核型特征变化。结果48例 CBF-AML 患者中,13例（27.1%）出现 c-Kit 错义突变,包括8号外显子突变5例,17号外显子突变8例。 t（8;21）AML 患者 c-Kit 基因突变发生率高于 inv（16）AML患者[33.3%（9／27）比19.0%（4／21）,P＜0.05]。1例（2.1%）患者 FLT3-ITD 突变,3例（6.3％）患者 FLT3-TKD 突变。RUNX1-RUNX1T1阳性附加染色体异常的发生率达25.9%（7／27）,其中性染色体缺失最为常见,CBFβ-MYH11阳性附加染色体异常发生率较低。结论在 CBF-AML 中 c-Kit 基因突变发生率高, RUNX1-RUNX1T1阳性的附加染色体异常易见,为研究个体化治疗提供了一定的参考。     

TET2合并DNMT3A突变及其他共存基因突变对急性髓系白血病患者预后的影响

  目的  探究TET2合并DNMT3A突变及其他共存基因突变对成人非M3型急性髓系白血病（acute myeloid leukemia,AML）患者预后的影响。  方法  回顾性分析2018年1月至2021年9月于南昌大学第一附属医院确诊的初治且行血液肿瘤相关突变基因外显子二代测序检测的512例成人 AML（非 M3 型）患者的临床资料,分析患者的临床特征、疗效及生存情况。  结果  本研究共纳入110例AML患者,TET2突变组64例,DNMT3A单突变组46例。男性50例（45.5%）,中位年龄54（15～79）岁。TET2基因突变频率为12.5%（64/512）,98.4%（63/64）患者突变基因数≥2个,每例患者平均合并5.2个突变基因。NPM1（43.8%）、DNMT3A（42.2%）、FLT3-ITD/TKD（40.6%）、CEBPA（26.6%）、TTN（20.3%）为TET2突变常见的共存突变基因。TET2合并DNMT3A突变患者初次诱导完全缓解（complete response,CR）率为46.2%,略低于TET2单突变患者的76.9%（P=0.077）,与DNMT3A单突变患者无显著性差异（P=0.952）。TET2合并DNMT3A突变患者的中位总生存（median overall survival,mOS）时间为9.5个月,明显低于TET2单突变患者（P=0.002）,而与DNMT3A单突变患者无显著性差异（P=0.414）。三者的中位无复发生存（median relapse- free survival,mRFS）时间无显著性差异（P>0.05）。在TET2突变背景下,合并K/NRAS突变患者的CR率为28.6%,明显低于无K/NRAS突变患者的75.0%（P=0.030）,合并FLT3-ITD突变患者的mOS明显短于无FLT3-ITD突变患者（P=0.030）。多因素分析显示年龄≥60岁、合并FLT3-ITD突变、初次诱导未达CR是影响TET2突变AML患者总生存时间（overall survival,OS）的独立危险因素,DNMT3A突变不影响TET2突变患者OS。  结论  TET2突变是AML患者常见突变,且常合并共存基因突变。共存基因突变与TET2突变共同影响AML患者预后。基于二代测序的基因突变检测对指导AML精确分层及精准治疗具有重要意义。      

急性髓系白血病患者FMS样酪氨酸激酶3基因内部串联重复突变的检测及其临床意义

目的 分析急性髓系白血病（AML）患者骨髓FMS样酪氨酸激酶3基因内部串联重复（FLT3／ITD）突变情况.方法 采用聚合酶链反应方法检测96例初发AML患者FLT3／ITD突变,分析FLT3／ITD阳性患者的临床特征.结果 96例AML患者中FLT3／ITD突变18例（18.8％）.其中M22例,M3 11例,M42例,M53例.FLT3／ITD阳性AML患者初发时外周血白细胞计数中位数为18.0×109／L（3.6× 109～ 137.6×109/L）,FLT3／ITD阴性AML患者为6.3×109/L（4.5×109 ～ 113.0×109/L）,两组比较差异有统计学意义（t=3.04,P＜0.05）.FLT3／ITD阳性者随访16例,中位随访时间10个月（6～ 15个月）,13例处于第1次完全缓解.诱导缓解率为81.3％（13／16）.结论 FLT3／ITD是AML患者常见的基因突变,FLT3／ITD阳性患者白细胞计数较高.     

Prognostic Relevance of DNMT3A,FLT3 and NPM1 Mutations in Syrian Acute Myeloid Leukemia Patients

Objective: Among all types of hematological neoplasms, acute myeloid leukemia (AML) has the highest death rate. Recently, cytogenetic and molecular genetics are crucial in the management, as a consequence of their effect on AML pathogenesis, classification, risk-stratification, prognosis and treatment. Methods: 100 Syrian adults with Normal Karyotype (NK) newly diagnosed  AML patients were included in this study, all cases confirmed histologically and immunohistochemically. Patients were divided into six subgroups using flow cytometry and cytological results. Polymerase chain reaction (PCR) was performed on exon 11-12 for FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), exon 12 for Nucleophosmin1 (NPM1), and exon 23 for DNA methyltransferase 3A (DNMT3A) using target primers, the electropherograms were analyzed for gene mutations by comparing with the reference DNA sequence. Data were compared and aligned with different sequences using the NCBI BLAST Assembled Genomes tool. Results: FLT3-ITD, NPM1 and DNMT3A were detected in 24%, 22 % and 4%  patients respectively. M2 subtype had the most frequent incidence of diagnosis in AML. FLT3-ITD mutation patients had the highest mean of death cases, while the DNMT3A mutation patients had the lowest. On the other hand, the highest mean of remission was in patients with NPM1 mutation and the lowest in the carriers of the FLT3-ITD mutation. It was observed that the mean relapsed patients with FLT3-ITD and DNMT3A mutation was 3.4 and 2 months respectively, with no significant differences between (FLT3-ITD and DNMT3A) carriers and non-carriers relapsed. On the contrary,  the mean relapsed for NPM1 mutation carriers was 2.4  months with significant statistical differences. The mean survival time for patients with FLT3-ITD and NPM1  mutation was 5.9 months and 5.85 months respectively, with significant correlation. Between it was 5.88 months in DNMT3A patients with no significant differences. Finally, It was noted that the mean event free survival (EFS) of FLT3-ITD mutation patients was 4.818 months and the mean EFS of NPM1 mutation patients was 4.805 months, with significant statistical differences (p<0.05) between the mutation patients and non-mutated patients regarding to EFS, While this mean was not statistically significant in patients carrying DNMT3A mutation. Conclusion: Patients with FLT3-ITD and NPM1 mutations have the worst prognosis, where the presence of those mutations was significantly related to overall survival (OS) and EFS. Our study reflects that DNMT3A was not an extremely bad prognostic effect as an independent factor. We can declare according to this study that genetic mutation and variants detection could easily be incorporated into the regimen evaluation of AML patients.     

FLT3 and NPM1 gene mutations in childhood acute myeloblastic leukemia

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. Mutations in fms-like tyrosine kinase 3 (FLT3) gene including internal tandem duplication (ITD) and point mutation in the tyrosine kinase domain (TKD) as well as in nucleoplasmin (NPM1) gene are associated with pathogenesis of acute myeloblastic leukemia (AML). Several reports have demonstrated high incidences of the FLT3 and NPM1 mutations in adult AML patients. Since the pathogenesis of pediatric AML is different from that of adult and the FLT3 and NPM1 mutations have not been well characterized in childhood AML. Therefore, the objective of this study was to determine the frequencies of FLT3 and NPM1 mutations in 64 newly diagnosed childhood AML patients. All blood and bone marrow samples were previously diagnosed with AML by using flow cytometry and/or cytochemistry. FLT3-ITD and FLT3-TKD were detected by PCR and PCR-RFLP methods, respectively. The NPM1 mutation was analyzed by PCR and direct DNA sequencing. The FLT3 mutations were detected in 7 of 64 (11.1%), including FLT3-ITD in 4 of 64 (6.3%) and FLT-TKD in 3 of 62 (4.8%). The NPM1 mutation was not detected in this cohort. By multivariate analysis, white blood cell counts, peripheral blood and bone marrow blast cell counts at diagnosis were significantly higher in children with FLT3-ITD (P<0.05). In addition, the median percentage of CD117 was significantly higher in leukemic blast cells with FLT3-ITD than those with wild type (P=0.01). We did not find any FLT3 mutations in children aged less than 5 years. The AML M3 cell type was most frequently associated with FLT3 gene mutations (50%). In conclusion, the FLT3 mutations was found in 11.1% but none of NPM1 mutation was detected in Thai children with AML. These data support the hypothesis of different biology and pathogenesis between adult and childhood AML.     

伴Fms样酪氨酸激酶3内部串联重复的急性髓系白血病临床特点及预后分析

目的 探讨Fms样酪氨酸激酶3内部串联重复(FLT3-ITD)的急性髓系白血病(AML)患者的临床特点及预后.方法 回顾性分析2011年6月至2014年3月收治的39例FLT3-ITD的AML患者临床资料.结果 FLT3-ITD突变的发生率为11.6％(39/337),39例FLT3-ITD AML患者中,M5所占比例最高(43.6％,17/39),其次为M2(28.2％,11/39);外周血白细胞计数平均为88.63×109/L,其中12例(30.8％)大于100×109/L;骨髓原始细胞比例平均为82.53％,其中33例(84.6％)大于50.00％.13例发生髓外浸润;17例核型正常,9例核型异常,3例未见核分裂象;13例患者伴随NPM1突变,2例伴有KIT突变,3例伴有DNMT3突变.37例接受治疗的患者中,第1个疗程获完全缓解(CR)16例(43.2％),第2个疗程获CR 4例(10.8％),2个疗程累积CR率为54.0％,诱导治疗相关病死率为21.6％ (8/37),死亡原因主要为感染及出血.中位随访时间12个月,20例CR患者的复发率为50.0％(10/20),无复发生存(RFS)率为45.0％(9/20);移植组17例患者的总生存及RFS均优于单纯化疗组的20例患者(P=0.004、0.020).结论 FLT3-ITD AML具有初发时外周血白细胞计数及骨髓原始细胞比例高、与M5亚型高度伴随的临床特点,异基因造血干细胞移植能明显提高患者总生存期及无复发生存期.     

Identification of FLT3 and NPM1 Mutations in Patients with Acute Myeloid Leukaemia

Objective: The most frequent acquired molecular abnormalities and important prognostic indicators in patientswith Acute Myeloid Leukaemia (AML) are fms-like tyrosine kinase-3 gene (FLT3) and nucleophosmin-1 (NPM1)mutations. Our study aims to develop a cost effective and comprehensive in-house conventional PCR method fordetection of FLT3-ITD, FLT3-D835 and NPM1 mutations and to evaluate the frequency of these mutations in patientswith cytogenetically normal (CN) AML in our population. Methods: A total of 199 samples from AML patients (95women, 104 men) were included in the study. Mutation analyses were performed using polymerase chain reaction(PCR) and gene sequencing. Result: Sixty-eight patients were positive for the mutations. FLT3-ITD mutations weredetected in 32 patients (16.1%), followed by FLT3-D835 in 5 (2.5%) and NPM1 in 54 (27.1%). Double mutations ofNPM1 and FLT3-ITD were detected in 23 cases (11.6%). Assays validation were performed using Sanger sequencingand showed 100% concordance with in house method. Conclusion: The optimized in-house PCR assays for thedetection of FLT3-ITD, FLT3-D835 and NPM1 mutations in AML patients were robust, less labour intensive and costeffective. These assays can be used as diagnostic tools for mutation detection in AML patients since identification ofthese mutations are important for prognostication and optimization of patient care.     

Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan,Northeast Peninsular Malaysia

Background: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferationvia activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most commongene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated withpoor prognosis. Materials and Methods: We performed mutational analysis of exons 14-15 and 20 of the FLT3gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencinganalysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan,Northeast Peninsular Malaysia. Results: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%)whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 ofthe juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blastpercentage (p-value = 0.008) and white blood cell count (p-value = 0.023) but there was no significant differencein median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value = 0.374). Conclusions: Theincidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Westernworld and has a significant association with WBC and blast percentage.     

Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype

Objective: Activating mutations of the fms-like tyrosine kinase 3 gene (FLT3) by internal tandem duplications (ITDs) in the juxtamembrane domain (JMD) have been reported in ~30% of adult acute myeloid leukemia (AML) patients with cytogenetically normal karyotype (CN). However, FLT3/ITD mutations are frequently accompanied with leukocytosis, high percentage of blasts in bone marrow (BM), and increased the risk of treatment failure in AML patients. FLT3-ITD mutated AML patients mainly with normal karyotype have higher relapse probability and shorter duration of complete remission (CR) after chemotherapy, so FLT3-ITD mutation is considered as an independent poor prognostic factor in AML. Methods: FLT3-ITD and FLT3-KTD were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism- PCR (RFLP-PCR) in 44 adults AML patients with cytogenetically normal karyotype (AML-CN) at diagnosis to characterize FLT3 status. The results were correlated with the prognostic factors. Results: In this study, FLT3-ITD mutations were identified in 7 (15.9%) of the 44 AML-CN patients. Among the 7 patients with FLT3/ITD mutations, 6 patients revealed a typical ITDs mutation (fragment size was 329 bp) and one patient showed untypical ITD mutation (fragment size was ~400 bp). Whereas 37 patients (61.7%) were FLT3-ITD. None of all AML-CN patients examined showed FLT3-KTD mutations. Conclusions: Our results support that FLT3-ITD are independent adverse prognostic factors for elderly AML-CN patients and are associated with low overall survival (OS), low rate of CR, high relapse rate (RR), and high percentage of BM blast at diagnosis. We concluded, FLT3 mutation analysis should be performed as a routine test in AML-CN patients.