| Budget Amount *help |
¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Outline of Final Research Achievements |
Somatic GATA1 gene mutations leading to the production of GATA1s that lacks the amino-terminal transactivation domain is both requisite and sufficient for the development of the preleukemic condition referred to as transient myeloproliferative disorder (TMD) for acute megakaryoblastic leukemia (AMKL) in Down-syndrome newborns. We have established mice exclusively expressing GATA1s which phenocopy the human TMD. In this research, we found that reduced apoptosis and increased proliferation capacities in GATA1s megakaryocyte progenitors are involved in the pathogenesis of TMD. We also found that megakaryocyte progenitors with relatively lower level of GATA1s reduced in differentiation potency, consequently the progenitors persistently stay in mice and the mice are prone to develop leukemia. Higher amount of GATA1s expression partially compensates the defect in megakaryocyte maturation mediated through the Ras signaling cascade and enable progenitors to pass quickly without transformation.
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