| Budget Amount *help |
¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000)
Fiscal Year 2018: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2017: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2016: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2015: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Outline of Final Research Achievements |
Chromosomal rearrangement between 3q21 and 3q26 provokes leukemia with poor prognosis. The rearrangement induces misexpression of both misexpression of EVI1 gene and reduction of GATA2 gene expression by translocation of the GATA2 gene enhancer. Here we asked whether GATA2 haploinsufficiency in addition to EVI1 misexpression contributed to leukemogenesis by using a 3q21q26 mouse model that recapitulates the GATA2 enhancer-driven EVI1 misexpression coupled with a Gata2 heterozygous deletion. Of note, the Gata2 heterozygous deletion promoted the EVI1-provoked leukemogenesis. While EVI1-misexpressed blast-like cells retained some limited ability to differentiate into myeloid cells, simultaneous loss of one Gata2 allele suppressed the myeloid differentiation and promoted the expansion of these blast-like cells. These results demonstrate that Gata2 heterozygous deletion accelerates EVI1 misexpression leukemia by inducing proliferation and differentiation defect of leukemia cells.
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