Role of GATA-2 in regulating inflammatory cytokine production

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16175
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: Onodera Koichi 東北大学, 医学系研究科, 助教 (80792291)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: GATA-2

Outline of Final Research Achievements

Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia and acute myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which is associated with increased susceptibility to viral infections. Because patients with GATA-2 deficiency syndrome could retain a wild-type copy of GATA-2, boosting residual wild-type GATA-2 activity may represent a novel therapeutic strategy for the disease. Here, we established a screening system to identify GATA-2 activators based on human U937 monocytic cells as a surrogate model of DC progenitor. In conclusion, our system represents a potential tool for identifying novel regulators of GATA-2, thereby contributing to the development of novel therapeutic approaches.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

MonoMAC症候群では片方のアリルのGATA2遺伝子変異によるGATA2タンパク質の量的異常を呈していることが原因であるため、野生型のGATA2の発現を誘導することが治療戦略の1つとなり得る。今回樹立したGATA2バイオアッセイ系を用いたスクリーニング法はGATA2遺伝子の上流制御機構の解明やMonoMAC症候群をはじめとする難治性疾患に対する新規治療薬の開発に一助となることが期待される。