ND4 mutations are more prevalent in patients with acute myeloid leukemia of M2 morphology

Abstract

Background: To evaluate the prognostic value of ND4 gene mutation and other gene mutations in acute myeloid leukemia (AML) patients, especially among those without karyotype abnormalities.Methods: We analyzed the biological and clinical characteristics of 460 newly diagnosed AML patients.The mutation status and prognostic impact in FLT3-ITD, NPM1, c-KIT, CEBPA, DNMT3A, and ND4 genes were investigated.Results: The frequency of ND4 gene mutation was 6.6%. ND4 mutations were prevalent in patients with AML of M2 morphology (P=0.001). About 11.3% patients were diagnosed with core binding factor (CBF) AML and c-KIT mutations were most commonly seen in CBF leukemia patients (16.2%). DNMT3A mutations were usually found in M5 but not in M4 (P=0.006 and 0.498, respectively). ND4 germline mutations in non-M3 patients included types of A131V, F149L, A404T, and Y409H, while one M3 patient had type of G242D somatic mutation. Patients with ND4 mutations were significantly associated with CD19 expression in non-M3 patients (P=0.045). Patients with ND4 germline mutations may have unfavorable survival, but showed no statistical significance in overall survival (OS) and relapse-free survival (RFS) between patients with germline ND4 mutations and wild-type (P=0.159 and 0.087, respectively). According to the molecular prognostic factors, patients with normal cytogenetic risk were divided into three groups in the OS and RFS analysis (P=0.017 and 0.025, respectively) as favorable mutational risk has favorable prognosis and unfavorable mutational risk has poor one.Conclusions: Conventional molecular and cytogenetic factors could divide AML patients into distinctive prognosis groups. ND4 mutations were prevalent in M2 patients and were associated with higher expression of CD19. Whether patients with germline ND4 mutations have poorer prognosis still needs to be confirmed.

A comprehensive assessment of the prognostic role of cell adhesion molecules in acute myeloid leukemia

“…Decisions about the choice of postremission therapy in patients with AML currently depend on the identification of a selected set of genetic markers at diagnosis and the detection of residual disease with multiparameter flow cytometry ( 3 ). Quantitative molecular evaluation during complete remission could further improve prognostication of outcomes in patients with AML ( 4 ). Emerging immunotherapies such as chimeric antigen receptor T cells have advanced the treatment of acute lymphoblastic leukemia ( 5 ); so far, most of the targets have been membrane proteins and members of cell adhesion molecule (CAM) sets ( 6 ).…”