The University of Tokyo · 의학
미네오 쿠로카와 교수의 연구실은 백혈병의 발병 기전을 규명하는 데 초점을 맞추고 있으며, 특히 AML1/RUNX1 단백질의 전사 조절 기전과 DNMT3A 돌연변이가 허혈성 줄기세포의 기능에 미치는 영향을 중심으로 연구를 진행하고 있습니다. TGF-β 신호 전달 경로의 억제나 DNA 메틸화 독립적 작용을 통해 백혈병 전구세포의 이상적 축적을 유도하는 분자 메커니즘을 밝혀내고 있으며, 전사 인자와 공억재단 단백질 간의 인산화 조절 메커니즘을 규명하고 있습니다. 이는 백혈병의 분자 기전 해소와 새로운 치료 전략 개발에 기여할 잠재력을 지닙니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
The t(3;21)(q26;q22) chromosomal translocation associated with blastic crisis of chronic myelogenous leukemia results in the formation of the AML1/Evi-1 chimeric protein, which is thought to play a causative role in leukemic transformation of hematopoietic cells. Here we show that AML1/Evi-1 represses growth-inhibitory signaling by transforming growth factor-beta (TGF-beta) in 32Dcl3 myeloid cells. The activity of AML1/Evi-1 to repress TGF-beta signaling depends on the two separate regions of th
Despite the clinical impact of DNMT3A mutation on acute myeloid leukaemia, the molecular mechanisms regarding how this mutation causes leukaemogenesis in vivo are largely unknown. Here we show that, in murine transplantation experiments, recipients transplanted with DNMT3A mutant-transduced cells exhibit aberrant haematopoietic stem cell (HSC) accumulation. Differentiation-associated genes are downregulated without accompanying changes in methylation status of their promoter-associated CpG islan
The AML1 (RUNX1) gene, one of the most frequent targets of translocations associated with human leukemias, encodes a DNA-binding protein that plays pivotal roles in myeloid differentiation through transcriptional regulation of various genes. Previously, we reported that AML1 is phosphorylated on two serine residues with dependence on activation of extracellular signal-regulated kinase, which positively regulates the transcriptional activity of AML1. Here, we demonstrate that the interaction betw
