| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
RUNX1 mutations have been shown to contribute to the development of myeloid neoplasms and are frequently identified in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) including chronic monocytic leukemia (CMML). The RUNX1 gene has several isoforms. We focused on both functional full-length isoforms RUNX1b and the short isoform RUNX1a. RUNX1a has a dominant negative effect on RUNX1b. We quantified expression levels of RUNX1 isoforms in CD34+ cells from patients with MDS/MPN. We found that RUNX1a was overexpressed in MDS/MPN patients, and that these levels of expression increased as the disease progressed. Furthermore, the aberrant splicing resulting in RUNX1a was shown to be caused by splicing factor mutations that are frequently detected in MDS/MPN. We demonstrated for the first time that in addition to RUNX1 mutations, overexpression of RUNX1a induced by splicing factor mutations may have an important role in disease progression in MDS/MPN patients.
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