TNFAIP3 mutation is an independent poor overall survival factor for patients with T‐cell acute lymphoblastic leukemia

BACKGROUND: It is imperative to explore potential biomarkers for predicting clinical outcome and developing targeted therapies for T‐cell acute lymphoblastic leukemia (T‐ALL). This study aimed to investigate the mutation patterns of tumor necrosis factor‐alpha‐inducing protein 3 (TNFAIP3, also known as A20) and its role in the prognosis of T‐ALL patients. METHODS: Polymerase chain reaction (PCR) and Sanger sequencing data from T‐ALL (n = 49, JNU) and targeted sequencing data from T‐ALL (n = 54, NFH) in our clinical center and a publicly available dataset (n = 121, PRJCA002270), were used to detect TNFAIP3 mutation. RESULTS: Three TNFAIP3 single nucleotide polymorphisms (SNPs; g.3033 C > T, g.3910 G > A, and g.3904 A > G) were detected in T‐ALL in the JNU dataset, and g.3033 C > T accounted for the highest proportion, reaching 60% (6/10). Interestingly, TNFAIP3 mutation mainly occurred in adults but not pediatric patients in all three datasets (JNU, NFH, and PRJCA002270). T‐ALL patients carrying a TNFAIP3 mutation were associated with a trend of poor overall survival (OS) (p = 0.092). Moreover, TNFAIP3 mutation was also an independent factor for OS for T‐ALL patients (p = 0.008). Further subgroup analysis suggested that TNFAIP3 mutation predicted poor OS for T‐ALL patients who underwent chemotherapy only (p < 0.001), and it was positively correlated with high risk and early T‐cell precursor ALL (ETP‐ALL) in two independent validation datasets (NFH and PRJCA002270). CONCLUSION: TNFAIP3 mutation mainly occurs in adult T‐ALL patients, and it was associated with adverse clinical outcomes for T‐ALL patients; thus, it might be a biomarker for prognostic stratification.