Next-generation sequencing-based genetic landscape and its clinical implications for Chinese acute myeloid leukemia patients.

ABSTRACT

BACKGROUND: Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous disease. The survival of older patients is generally poor. In the current study, we sought to investigate the differences in molecular gene mutations between younger and older AML patients, and to identify those newly diagnosed AML patients who are more likely to respond to standard cytarabine and daunorubicin induction chemotherapy. METHODS: We retrospectively evaluated 179 patients who were newly diagnosed with non-M3 AML. A next-generation sequencing assay covering 34 genes was used to investigate recurrently mutated genes. The mutational status of fusion genes was determined by real time PCR. RESULTS: The median age at diagnosis was 53 years (range 18-88 years). Sixty-eight patients were 60 years or older with a median age of 67 years (range 60-88 years). Eighteen patients (10.1%) carried t(8;21)(q22;q22.1) or RUNX1-RUNX1T1 gene fusion, and there was a significantly higher incidence in younger patients (p = 0.019). At least one non-synonymous gene mutation was detected in 159 patients (88.8%). The median number of gene mutations was two (range 0-6). The mean number of molecular gene mutations at diagnosis was higher in older patients than younger patients (2.5 vs 1.83, p = 0.003). Older patients had significantly higher incidences of ASXL1 (22.1% vs 13.5%, p = 0.025) and TP53 mutations (13.2% vs 3.6%, p = 0.034). In total, 78 patients received DA60 (daunorubicin 60 mg/m2 per day on days 1-3 and cytarabine 100 mg/m2 twice per day on days 1-7) as the induction therapy, and information was available on their response to induction treatment. Patients with RUNX1-RUNX1T1 gene fusion were significantly more likely to achieve complete remission (CR) after DA60 induction therapy (p = 0.026), as were patients without the ASXL1 mutation (p = 0.007). CONCLUSION: Older AML patients had a lower incidence of favorable cytogenetics and higher frequencies and burdens of molecular mutations that are associated with poor prognosis compared to younger patients. Patients with RUNX1-RUNX1T1 gene fusion or without the ASXL1 gene mutation had a better chance of achieving CR when treated with cytarabine and daunorubicin induction chemotherapy.