Low frequency and variability of FLT3 mutations in Korean patients with acute myeloid leukemia

FLT3 mutations are common genetic changes, and are reported to have prognostic significance in acute myeloid leukemia (AML). The FLT3 internal tandem duplication (ITD) and the D835 activating mutation in the tyrosine kinase domain (TKD) were analyzed by polymerase chain reaction (PCR) in the genomic DNA of Korean patients with AML at diagnosis and during follow-up. There were 226 patients with AML enrolled between March 1996 and August 2005. The incidence of ITD and TKD at diagnosis was 13% (29/226) and 3% (6/226). When compared to Western and other Asian patients with AML, Korean patients had a lower frequency by about two-thirds of ITD and TKD. Among the non-M3 cases (N=203), the patients with an ITD had a significantly shorter event-free survival when compared with those without an ITD (p=0.0079). Among 54 relapsed patients, 9 patients had the FLT3 ITD at diagnosis. Six patients demonstrated a reappearance of the ITD and 3 patients remained negative at relapse. One patient, among 45 patients who relapsed, had a negative baseline ITD but acquired a de novo ITD at relapse. There were 101 samples from 93 patients in remission; they were all negative for an ITD. Among 34 patients who failed to achieve a remission, five patients had a persistent ITD and one patient had a de novo ITD. These results support the concept of resistance of FLT3 ITD leukemic clones to chemotherapy. Therefore, effective therapy with FLT3 targeting agents may improve the prognosis of non-M3 AML patients with the FLT3 mutation.     

FLT3 and NPM1 mutations in myelodysplastic syndromes: Frequency and potential value for predicting progression to acute myeloid leukemia

We reviewed FLT3 and NPM1 mutation data in a large cohort of patients with myelodysplastic syndrome (MDS). The frequencies of FLT3 and NPM1 mutation were 2.0% and 4.4%, respectively, and mutations were restricted to cases of intermediate- and high-risk MDS. Cytogenetic abnormalities were identified in 46.9% of cases. FLT3 mutations were associated with a complex karyotype (P = .009), whereas NPM1 mutations were associated with a diploid karyotype (P < .001). FLT3 mutation (P < .001) was associated with progression to acute myeloid leukemia (AML), as were a higher bone marrow (BM) blast count (P < .001) and complex cytogenetics (P = .039). No patient with an NPM1 mutation alone had disease that progressed to AML. Cox proportional regression multivariate analysis indicated that FLT3 mutation, NPM1 mutation, complex cytogenetics, BM blast count, pancytopenia, and age were independent factors that correlated with progression-free survival. We conclude that FLT3 and NPM1 mutations are rare in MDS, but assessment of mutation status is potentially useful for predicting progression to AML.     

Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations

Systematic assessment of minimal residual disease (MRD) in acute myeloid leukemia (AML) patients has been hampered by lack of a reliable, uniform MRD marker applicable to all patients. We evaluated next-generation sequencing (NGS) for MRD assessment in AML patients (n = 80 samples). The ability of NGS technologies to generate thousands of clonal sequences makes it possible to determine the allelic ratio of sequence variants. Using NGS, we were able to determine the allelic ratio of different FLT3-internal tandem duplication (ITD) clones within one patient sample, in addition to resolution of FLT3-ITD insertion site, length, and sequence in a single analysis. Furthermore, NGS allowed us to study emergence of clonal dominance. Parallel assessment of MRD by NGS and quantitative real-time polymerase chain reaction in NPM1 mutated patients was concordant in 95% of analyzed samples (n = 38). The frequency of mutated alleles was linearly quantified by NGS. As NGS sensitivity is scalable depending on sequence coverage, it reflects a highly flexible and reliable tool to assess MRD in leukemia patients.     

一种同时检测急性髓系白血病FLT3-ITD和NPM1基因突变的快速和简便方法

目的 建立用聚丙烯酰胺凝胶电泳法(polyacrylamide gel electrophoresis,PAGE)同时快速检测正常核型急性髓细胞白血病(cytogenetically normal acute myeloid leukemia,CN-AML)患者FLT3-ITD 和NPM1基因突变的方法.方法 在多重PCR基础上,用毛细管电泳法(capillary electrophoresis,CE)和PAGE凝胶电泳法同时检测117例初发CN-AML患者的FLT3-ITD和NPM1基因突变.结果 突变型双链DNA分子,如突变型FLT3和NPM1的长度均比野生型长(FLT3 -mut:420 bp＞FLT3-wt:327～332 bp,NPM1 -mut:172 bp＞ NPM1 -wt:168 bp),因此,在PAGE凝胶电泳中突变双链DNA比未突变的DNA移动得慢,从而可将突变检出.117例CN-AML患者均通过CE检测得到验证,其结果与PAGE凝胶电泳结果完全一致(FLT3-ITD +/NPM1-患者18例,占15.4％; FLT3 ITD +/NPM1+患者19例,占16.2％;FLT3-ITD -/NPM1+患者25例,占21.4％;FLT3-ITD -/NPM1-患者55例,占47.0％).结论 两种电泳法均可快速、简便地同时检测CN-AML患者FLT3- ITD和NPM1基因突变.CE检测敏感,图像清晰;PAGE凝胶电泳法则操作简单,成本低,结果可靠,更适于在基层医院开展初步筛查.     

骨髓增生异常综合征巨噬细胞增生与造血细胞凋亡的相关性

目的 观察骨髓增生异常综合征(MDS)巨噬细胞增生状况与原位细胞凋亡的相关性并探讨其意义。方法 用碱性磷酸酶-抗碱性磷酸酶免疫酶标(APAAP)技术(CD68抗原标记)结合DNA末端原位标记(ISEL)分析30例MDS患者(其中低危组21例、高危组9例)骨髓塑料冷包埋切片中巨噬细胞数量和造血细胞原位凋亡状况,并分析二者间的相关性。缺铁性贫血(IDA)12例作对照。结果 (1)MDS患者骨髓切片中CD68阳性细胞数为(29.2±33.0)/mm~2,对照组为(21.2±16.7)/mm~2(P>0.05);(2)MDS病例凋亡细胞数平均为(71.5±70.9)/mm~2,对照组为(37.3±23.0)/mm~2(P<0.05);(3)MDS低危组CD68阳性细胞[(35.5±37.0)/mm~2]和凋亡细胞数[(90.7±74.6)/mm~2]均高于高危组[(14.6±11.7)/mm~2和(26.8±33.1)/mm~2](P分别<0.05和<0.01);(4)MDS病例CD68阳性细胞数与造血细胞凋亡显示显著正相关;r=0.83,P<0.001;(5)MDS病例骨髓切片中CD68阳性细胞与凋亡细胞不显示位置上的相关性;(6)MDS病例CD68阳性细胞本身存在过度凋亡。结论 MDS存在过度凋亡;MDS低危组凋亡高于高危组;MDS巨噬细胞与造血细胞凋亡具有相关性。     

Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD

This study is aimed to investigate the pattern of CEBPA mutations and its clinical significance in Chinese non-M3 acute myeloid leukemia (AML) patients. The entire coding region of CEBPA gene was amplified by PCR and then sequenced in samples from 233 non-M3 AML patients. Fifty mutations were identified in 37 (15.8%) patients with eleven (4.7%) double mutated CEBPA (dmCEBPA) and twenty-six (11.1%) single mutated CEBPA (smCEBPA). dmCEBPA was exclusively observed in M1 and M2 subtypes of FAB classification (P = 0.008), whereas smCEBPA occurred in almost all subtypes (P = 0.401). Patients with dmCEBPA had significantly younger age and higher WBC counts than those with wtCEBPA (P = 0.016 and 0.043, respectively). Both dmCEBPA and smCEBPA were mainly present in cytogenetically normal patients. Patients with dmCEBPA achieved higher rate of complete (CR) than wtCEBPA patients (88% vs. 51%, P = 0.037), whereas smCEBPA and wtCEBPA groups are similar (47% vs. 51%, P = 0.810). Patients with dmCEBPA had a superior overall survival (OS) compared with patients with wtCEBPA (P = 0.033), whereas patients with smCEBPA had a similar OS as patients with wtCEBPA (P = 0.976). dmCEBPA but not smCEBPA was also associated with favorable outcome in patients with wild-type NPM1 and FLT3-ITD (NPM1^wtFLT3-ITD^wt). Our data confirm that dmCEBPA but not smCEBPA is prognostically favorable in NPM1^wtFLT3-ITD^wt AML, and suggest that the entity AML with mutated CEBPA should be definitely designated as AML with dmCEBPA in WHO classification and smCEBPA should be excluded from the favorable risk of molecular abnormalities.     

白血病患儿骨髓间充质干细胞与白血病细胞株K562/AO2生长增殖及凋亡的相关性

背景:骨髓微环境是白血病的发病根源,微环境的改变对白血病细胞的生物学行为和性能有一定的影响。目的:探讨白血病患儿骨髓间充质干细胞对K562/AO2细胞生长增殖及凋亡的影响。方法:体外环境下进行K562/AO2细胞单独悬浮培养,K562/AO2细胞与白血病患儿骨髓间充质干细胞共培养。锥虫蓝染色计数活细胞数,描绘两组细胞生长曲线,PI单染法检测细胞周期,Annexin V/PI法检测细胞凋亡情况。结果与结论:(1)单独培养组前3 d细胞生长未出现明显改变,第4天开始细胞增殖速度明显加快,并于培养第6天达到最高峰。共培养组整体增殖曲线较为平缓,无明显的增殖高峰;(2)单独培养组的G0-G1期细胞比例显著低于共培养组,S期细胞比例显著高于共培养组(P<0.05)。两组G2-M期细胞比例差异无显著性意义;(3)单独培养组的细胞凋亡数显著高于共培养组(P<0.05);(4)结果表明,与白血病患儿骨髓间充质干细胞共培养后K562/AO2细胞生长受到抑制,细胞周期阻滞在G0-G1期,且会对K562/AO2细胞凋亡产生抵抗作用。     

Examination of the FLT3 and NPM1 mutational status in patients with acute myeloid leukemia from southeastern Poland

Introduction

Acute myeloid leukemia (AML) is a genetically heterogeneous disease at both the cytogenetic and molecular levels. In AML cells many chromosomal aberrations are observed, some of them being characteristic of a particular subtype of patients, and others being less significant. Besides chromosomal abnormalities, the leukemic cells can have a variety of mutations involving individual genes. The aim of this work was to investigate the frequencies of molecular alterations with the focus on FLT3-ITD and NPM1 mutations in AML patients of different age groups living in a southeastern region of Poland.

Material and methods

The study group comprised 50 consecutive AML patients. We analyzed bone marrow samples by conventional cytogenetics. Cytogenetic evaluation in selected cases was complemented by the FISH technique. The internal tandem mutation in the FLT3 gene was identified using polymerase chain reaction (PCR), and the NPM1 mutation was assessed by direct nucleotide sequencing.

Results

The studies using classical cytogenetics showed chromosomal aberrations in 32 (64%) patients. In 18 cases no changes in the karyotype were found by conventional karyotyping. FLT3-ITD mutation was detected in 4 (8%) patients and mutation of NPM1 in 3 patients with AML (6%).

Conclusions

The incidence of both mutations in our study group was lower than described elsewhere. We have confirmed that FLT3-ITD occurred more commonly in older patients and it was associated with shorter overall survival. By contrast, mutation of exon 12 of the NPM1 gene seems to be a good prognostic factor in AML patients with normal karyotype.     

Chromosome analyses in patients with myelodysplastic syndromes: Correlation with bone marrow histopathology and prognostic significance

Summary Chromosome analyses of bone marrow and peripheral blood cells were performed in a total of 51 patients with myelodysplastic syndromes (MDS) simultaneously with histopathological examination of resinembedded bone marrow biopsies. Diagnosis of MDS was established by histopathology according to the French-American-British (FAB) classification, and reassessed by haematological data and clinical course. Clonal karyotypic changes were found in 30 of the 51 patients (59%): in 15 of 19 (79%) patients with refractory anaemia, 7 of 11 (64%) with refractory anaemia and excess of blasts (RAEB), 6 of 10 (60%) with RAEB in transformation, and 2 of 11 (18%) with chronic myelomonocytic leukaemia. The following three features of the histopathology revealed positive correlations with karyotype abnormalities: all cases of myelofibrosis in MDS (7/51) were accompanied by chromosome aberrations, microforms of megakaryocytes with reduced nuclear lobulation were observed in 18 of 30 cases with karyotype changes, and hypocellularity of haematopoiesis was associated with aberrations of chromosome 7 in 2 of 4 cases. No positive correlations were revealed between abnormal karyotypes and the transformation to acute leukaemia. The survival times were significantly decreased in patients with complex (3 and more) karyotype changes, when compared with patients with single (1–2) chromosome aberrations or normal karyotype, independently of the FAB classification.     

儿童急性淋巴细胞白血病患者HLA-A,B,DRB1等位基因多态性研究

目的　研究北方汉族人群儿童急性淋巴细胞性白血病 (ALL)患者与HLA A ,B ,DRB1等位基因多态性的遗传关联。方法　采用聚合酶链反应 序列特异性寡核苷酸探针 (PCR SSO)方法 ,对 197例北方汉族儿童ALL患者和 5 84 1例健康脐带血样本HLA A ,B ,DRB1等位基因多态性进行研究。结果　在HLA A ,B ,DRB1等位基因中 ,儿童ALL患者的A11(18.5 3% ,χ2 =8.5 9,P <0 .0 1,RR =1.4 7,EF =0 .0 6 35 )和A2 4 (19.2 9% ,χ2 =11.6 5 ,P <0 .0 1,RR =1.5 6 ,EF =0 .0 738) ;B4 0(18% ,χ2 =1199.6 2 ,P <0 .0 0 1,RR =5 3.2 3,EF =0 .18) ,B15 (30 % ,χ2 =15 9.17,P <0 .0 0 1,RR =9.6 89,EF =0 .0 14 ) ,B5 6 (1.5 % ,χ2 =16 .17,P <0 .0 0 1,RR =5 .92 ,EF =0 .0 774 ) ,B6 7(2 .5 % ,χ2 =5 .93,P <0 .0 1,RR =2 .74 ,EF =0 .0 774 ) ,和B2 7(3.75 % ,χ2 =4 .96 ,P <0 .0 1,RR =1.81,EF =0 .0 774 ) ;DR9(18.2 1% ,χ2 =16 .0 7,P <0 .0 0 1,RR =1.74 ,EF =0 .0 774 ) ,DR12(14 .13% ,χ2 =7.12 ,P <0 .0 1,RR =1.5 2 3,EF =0 .0 4 9) ,DR14 (7.88% ,χ2 =5 .194 ,P <0 .0 5 ,RR =1.5 74 ,EF =0 .0 2 87) ,和DR16 (4.89% ,χ2 =8.5 2 7,P <0 .0 1,RR =2 .0 6 5 ,EF =0 .0 2 5 )等基因的基因频率都显著高于正常人群     

PI3K/Akt和JAK2/STAT3信号转导通路在SO_2抗大鼠肢体缺血再灌注致急性肺损伤中的作用

目的:探讨PI3K/Akt和JAK2/STAT3信号转导通路在二氧化硫(SO2)抗肢体缺血再灌注(I/R)致急性肺损伤中的作用。方法:应用双大腿根部绑扎止血带复制大鼠双后肢缺血再灌注肺损伤模型。在再灌注前20 min腹腔注射Na2SO3/Na HSO3;在再灌注前1 h静脉注射Stattic或LY294002。应用TUNEL、ELISA、Western blot等方法检测细胞凋亡、细胞因子表达及相关信号通路蛋白表达的情况。结果:与对照组相比,I/R组的MDA及MPO含量、肺系数、细胞凋亡指数、细胞因子表达以及p-STAT3、p-Akt蛋白的水平均显著增高;当应用Na2SO3/Na HSO3后,上述反映肺损伤的各项指标均下降。Western blot检测结果显示I/R后,肺组织中p-STAT3和p-Akt蛋白的水平均明显增加。而应用Na2SO3/Na HSO3后,p-Akt蛋白的水平继续增加,但p-STAT3蛋白的水平却减少(P0.05)。结论:JAK2/STAT3和PI3K/Akt信号通路都参与了SO2抗肢体缺血再灌注致急性肺损伤的作用。JAK2/STAT3通路的活化,能够使I/R损伤加重;相反,PI3K/Akt信号通路的活化,可以使I/R损伤减弱。此外,JAK2/STAT3和PI3K/Akt信号通路之间存在交互作用。     

Screening for MECP2 mutations in Spanish patients with an unexplained mental retardation

Rett syndrome (RTT) is an X-linked progressive encephalopathy. Mutations in the MECP2 (methyl-CpG-binding protein) gene have been found to cause RTT. In the past few years, the role of MECP2 mutations in patients with mental disorders other than RTT has been studied, finding that mutations in MECP2 also contribute to non-syndromic entities. More recently, it has been demonstrated that RTT shares clinical features with those of Angelman syndrome, another neurodevelopmental disorder. These observations must be confirmed in a large series, to better understand the criteria needed for justifying a molecular test. Consequently, we have searched for MECP2 mutations in 294 patients (43 Angelman and Prader-Willi like included) with mental retardation (MR) of unknown aetiology. We found six polymorphisms (three novel, three previously reported) in 10 patients, one novel unclassified silent change (p.V222V) in a man, and one causative mutation in a girl with MR. Once this case was clinically reviewed, the girl presented symptoms of atypical RTT. The mutation (p.Y141C) lies within the methyl-binding domain, and has only been reported once in another atypical RTT. Our results show that the MECP2 mutations account for a low frequency (1/416 chromosomes = 0.24%) among mentally retarded individuals, which imply that it is necessary to perform an exhaustive clinical examination of patients before determining whether analysis of MECP2 is required or not.     

Outcome of allogeneic hematopoietic stem cell transplantation for cytogenetically normal AML and identification of high‐risk subgroup using WT1 expression in association with NPM1 and FLT3‐ITD mutations

According to recent guidelines, cytogenetically normal acute myeloid leukemia (CN AML) is divided into four molecular subgroups based on nucleophosmin‐1 (NPM1) and FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) mutations. All subgroups except for isolated NPM1mut are associated with poor prognosis. We retrospectively analyzed 223 patients with CN AML, 156 of whom were treated with standard chemotherapy. For postremission therapy, patients with available donors underwent allogeneic (allo) hematopoietic stem cell transplantation (HSCT) and the rest were treated with autologous HSCT or chemotherapy alone. We first compared the 4 conventional molecular subgroups, and then created another 4 subgroups based on WT1 expression: isolated NPM1mut, NPM1wt/FLT3‐ITD‐neg with low WT1 or high WT1, and FLT3‐ITD‐pos CN AML. We finally evaluated 89 patients who were treated with allo HSCT and achieved complete remission after standard chemotherapy. FLT3‐ITD CN AML showed the worst outcome irrespective of NPM1mut, and isolated NPM1mut CN AML showed no significant differences compared with NPM1wt/FLT3‐ITD‐neg CN AML. In contrast, two newly stratified low‐risk subgroups (NPM1wt/FLT3‐ITD‐neg with low WT1 and isolated NPM1mut CN AML) showed higher remission rates with superior overall survival (OS) compared with the other two high‐risk subgroups, which showed a higher relapse rate even after allo HSCT. Further analysis showed that higher pre‐HSCT expression of WT1 resulted in a higher relapse rate and poorer OS after allo HSCT. For CN AML, a risk‐adapted approach using allo HSCT with novel agents should be evaluated with stratification specified by WT1. © 2015 Wiley Periodicals, Inc.     

Analysis of the CFTR gene in the Spanish population: SSCP-screening for 60 known mutations and identification of four new mutations (Q30X,A120T, 1812-1 G→A,and 3667de14)

In order to determine the spectrum of CF mutations in the Spanish population, we have analysed 40 unrelated Spanish CF patients, with at least one chromosome negative for mutations ΔF508, G542X, and N1303K. Exons l–7,10–14a,15,16,17b,18–21 of the CFTR gene were studied by Single Strand Conformation Polymorphism (SSCP) analysis, using 60 known CF mutations as controls. SSCP screening allowed us to detect 28 different mutations in 52 CF chromosomes, and to identify four new mutations (Q30X in exon 2, A120T in exon 4, 1812-lG→A in intron 11 and 3667del4 in exon 19). Further analysis of the four new mutations in a total of 950 Spanish CF chromosomes showed a final frequency of 0.4%, 0.1%, 0.1%, and 0.1% for 1812-1G→A, Q30X, A120T, and 3667del4, respectively. No mutations were detected in exons 1, 3, 14a, 16, and 18. We have also detected 10 intragenic polymorphisms and DNA sequence variants and have analysed their frequencies in our population. The total of 28 mutations identified in the 80 CF chromosomes highlight the molecular heterogeneity of CF in the Spanish population. © 1994 Wiley-Liss, Inc.     

Reversal of FLT3 mutational status and sustained expression of NPM1 mutation in paired presentation, and relapse samples in a patient with acute myeloid leukemia

We report a case of de novo acute myeloid leukemia (AML) with unstable FLT3 gene mutations and stable NPM1 mutation. FLT3/D835 and NPM1 (Type A) mutations were detected upon diagnosis. During the relapse, the FLT3/D835 mutation changed to an FLT3/ITD mutation while the NPM1 (Type A) mutation was retained. Cytogenetic analyses showed the normal karyotype at diagnosis and relapse. Our findings raise interesting questions about the significance of these mutations in the leukemogenic process, about their stability during the evolution of the disease, and regarding the selection of appropriate molecular markers for the monitoring of minimal residual disease.     

Megalencephaly syndromes associated with mutations of core components of the PI3K‐AKT–MTOR pathway: PIK3CA,PIK3R2, AKT3, and MTOR

Megalencephaly (MEG) is a developmental abnormality of brain growth characterized by early onset, often progressive, brain overgrowth. Focal forms of megalencephaly associated with cortical dysplasia, such as hemimegalencephaly and focal cortical dysplasia, are common causes of focal intractable epilepsy in children. The increasing use of high throughput sequencing methods, including high depth sequencing to more accurately detect and quantify mosaic mutations, has allowed us to identify the molecular etiologies of many MEG syndromes, including most notably the PI3K‐AKT‐MTOR related MEG disorders. Thorough molecular and clinical characterization of affected individuals further allow us to derive preliminary genotype–phenotype correlations depending on the gene, mutation, level of mosaicism, and tissue distribution. Our review of published data on these disorders so far shows that mildly activating variants (that are typically constitutional or germline) are associated with diffuse megalencephaly with intellectual disability and/or autism spectrum disorder; moderately activating variants (that are typically high‐level mosaic) are associated with megalencephaly with pigmentary abnormalities of the skin; and strongly activating variants (that are usually very low‐level mosaic) are associated with focal brain malformations including hemimegalencephaly and focal cortical dysplasia. Accurate molecular diagnosis of these disorders is undoubtedly crucial to more optimally treat children with these disorders using PI3K‐AKT–MTOR pathway inhibitors.     

Oncogenic HRAS mutations cause prolonged PI3K signaling in response to epidermal growth factor in fibroblasts of patients with Costello syndrome

Costello syndrome (CS) is a rare congenital disorder characterized by failure to thrive, craniofacial dysmorphisms, cardiac and skin abnormalities, mental retardation, and predisposition to malignancies. CS is caused by heterozygous gain‐of‐function mutations in HRAS that also occur as somatic alterations in human tumors. HRAS is one of the three classical RAS proteins and cycles between an active, GTP‐ and an inactive, GDP‐bound conformation. We used primary human skin fibroblasts from patients with CS as a model system to study the functional consequences of HRAS mutations on endogenous signaling pathways. The GTP‐bound form of HRAS was significantly enriched in CS compared with normal fibroblasts. Active HRAS is known to stimulate both the RAF‐MEK‐ERK and the PI3K–AKT signaling cascade. Phosphorylation of MEK and ERK was normal in CS fibroblasts under basal conditions and slightly prolonged after epidermal growth factor (EGF) stimulation. Interestingly, basal phosphorylation of AKT was increased yet more in CS fibroblasts. Moreover, AKT phosphorylation was diminished in the early and enhanced in the late phase of EGF stimulation. Taken together, these results document that CS‐associated HRAS mutations result in prolonged signal flux in a ligand‐dependent manner. Our data suggest that altered cellular response to growth factors rather than constitutive activation of HRAS downstream signaling molecules may contribute to some of the clinical features in patients with CS. Hum Mutat 0,1–11, 2008. © 2008 Wiley‐Liss, Inc.     

SETBP1 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome

Background

Somatic mutations in SETBP1 gene have recently been detected in hematologic malignancies. The present study aimed to explore the frequency and clinical correlations of SETBP1 mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).