September 13 2021
We would like to inform you that the 72nd IRCMS seminar has been scheduled as below. We would be pleased to see many of you participating in the seminar.
Date : September 27, 2021 (Monday)
Time : 16:00-17:00
* To prevent the spread of COVID-19, it will be a Zoom-based online seminar.
Speaker : Yoshihiro Hayashi, MD, PhD
Laboratory of Oncology,
Tokyo University of Pharmacy and Life Sciences
Tilte : Dysregulated mitochondrial dynamics as a critical mediator of MDS ineffective hematopoiesis
Myelodysplastic syndromes (MDS) are one of the most complex hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis in which clonal progenitor expansion coexists with impaired myelopoiesis and excessive cell death. Chronic-sterile-inflammation is also a characteristic hallmark of MDS pathogenesis. Recently, we have demonstrated that overwhelming mitochondrial fragmentation in mutant HSCs and progenitors (HSC/Ps) triggers ineffective hematopoiesis in MDS. Based on previously unreported co-mutations in MDS patients, we established a useful preclinical tool that recapitulates bona fide MDS phenotypes and gene expression profiles. Notably, we focused unbiased transcriptome analysis on determining the distinct underlying mediator(s) of MDS etiology, and identified dysregulated mitochondrial dynamics as a critical mediator of MDS ineffective hematopoiesis.
A growing body of evidence shows that dysregulated mitochondrial dynamics contribute to immune-cell regulation, cell deaths, and pathogenesis of multiple diseases including cancers. We showed that DRP1-dependent mitochondrial fragmentation in mutant HSC/Ps causes inflammatory signaling activation in entire MDS clone, leading to dysplasia formation, impaired myelopoiesis, and cytopenia. We confirmed the excessive mitochondrial fission in patients with MDS regardless of mutational profile. Importantly, in vivo pharmacological inhibition of DRP1 activity rescued ineffective hematopoiesis phenotype and prolonged survival of MDS mice, suggesting that mitochondrial fragmentation could be a fundamental trigger of MDS pathogenesis. These findings provide new insights into mechanistic basis of ineffective hematopoiesis, and a clue for targeting ineffective hematopoiesis in MDS.
Anyone in Kumamoto University who wants to join is welcome; however, please pre-register by the following URL to secure your seat or receive the Zoom meeting information.
Flyer: (Click for a larger image)