Contribution of MIR9 on Disease Progression of Chronic Myelogenous Leukemia

We have reported that MIR9, a microRNA, is overexpressed in leukemic cells derived from a certain fraction of patients with acute myeloid leukemia (AML). The aberrant expression confers poor clinical course. These lines of our evidence suggest that overexpression of MIR9 in leukemic blasts stimulates further malignant transformation in leukemic cells. This made us analyze expression levels of MIR9 in the bone marrow cells from patients with chronic myelogenous leukemia. Among 25 patients analyzed, (chronic phase (CP): n=19, accelerated phase (AP): n=1, myeloblastic phase (BP): n=5), three in BP showed aberrantly high expression of MIR9, while none of them in CP or AP did. Furthermore, we performed targeted sequencing on the genomic DNA derived from the bone marrow cells of the same series of patients to screen for known mutations in 104 genes associated with myeloid malignancies. As a result, four patients (80%) in BC showed some numbers of gene mutations (one mutation in one patients, and two, three and six mutations in one each patient), while only four patients (21%) in CP revealed up to 2 gene mutations. Mutations in epigenetics-regulating genes such as DNMT3A were detected in patients in both CP and BP, but those in BCOR, CBL, NRAS and TP53 were only in BP. In addition, aberrant MIR9 expression was associated with multiple gene mutations in two patients in BC. These data suggested that overexpression of MIR9 could at least partly contribute to disease progression of CML.

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