ND4 mutations are more prevalent in patients with acute myeloid leukemia of M2 morphology
TRANSLATIONAL CANCER RESEARCH(2018)
摘要
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.
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关键词
Acute myeloid leukemia (AML),ND4 gene,gene mutation,prognosis
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