Impact Of TET2 Mutations And An TET2 Single Nucleotide Polymorphism In Cytogenetically Normal Acute Myeloid Leukemia

【Objective】To analyze the frequency and prognostic impact of TET2 mutations and a known single nucleotide polymorphism (SNP) located in the exon 11 of the TET2 gene in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers.【Methods】Mononuclear cells in bone marrow samples were collected from 192 patients with newly diagnosed AML. Polymerase chain reaction (PCR) and direct sequencing were used to sequence exon 3 to 11 of TET2 gene. The clinical and lab data of these cases were collected, and their clinical characteristics therapies and survival Prognosis were then analyzed. Mutations in NPM1, FLT3, MLL-PTD, IDH1and JAK2V617F were analyzed. TET2 SNP rs2454206 was analyzed in 100 healthy volunteers.【Results】1. TET2 mutation was detected in 25/192 (13.0%) AML patients (95% confidence interval [CI] 6.70-20.38 patients). The age median was 54 years old in mutated patients versus 41 years old in unmutated patients ( P=0.0131). Mutated and unmutated patients did not significantly differ in sex,initial clinical, hematologic parameters or subtype, except a difference with hemoglobin level 84 (70～108) g/L in mutated group versus 70 (55～87) g/L in unmutated group was noted( P=0.032). The correlations between TET2 alterations and FLT3, JAK2V617F ,C-KIT,IDH1 mutations were not identified except NPM1 mutations. TET2 mutated patients were associated with lower CR rate and OS in patients with cytogenetically normal acute myeloid leukemia (CN-AML).2. Polymerase chain reaction (PCR) and direct sequencing were used to sequence exon 3 to 11 of TET2 gene. 5 different previously annotated single nucleotide polymorphisms (SNPs) Were identified Presence of each SNP as a group were correlated with disease characteristics and clinical outcome, we found one SNP correlated significantly with outcome. SNP rs2454206 (TET2AG/GG )was found in 42.1% of CN-AML patients and 38.0% of healthy volunteers. TET2 SNP rs2454206 had lower WBC counts (P =0.037), higher hemoglobin level (P<0.01). We demonstrate that the CN-AML patients with SNP rs2454206(TET2AG/GG ) have a significantly better overall survival (OS) and relapse-free survival (RFS) than those without with SNP rs2454206. the SNP rs2454206 (TET2AG/GG ) may be an independent good prognostic factor among the CN-AML group Patients.【Conclusions】We conclude that TET2 mutations in AML are more prevalent in older patients and TET2 mutations was impact on clinical characteristics and may represent a molecular marker for poor prognosis in CN-AML. TET2 SNP rs2454206(TET2AG/GG ) may be a novel independent favorable-risk marker in CN-AML patients that might improve risk and treatment stratification.