Mitochondrial Dynamics as a Therapy Target in MDS
Abstract
Our project addresses both Fiscal Year 2021 Bone Marrow Failure Research Program Focus Areas, as it both attempts to understand the causes and progression of BMF diseases (Aim 1) and identify effective BMF treatments (Aim 2). Myelodysplastic syndromes are a group of disorders caused by dysfunctional bone marrow blood cells, which frequently progress to secondary acute myeloid leukemia (sAML). Besides allogeneic stem cell transplantation, currently, only hypomethylating agents (HMAs) are preferable treatments for these patients. However, HMAs have side effects that can be hard to bear, emphasizing the need that MDS patients acquire better therapeutic options. A revolution in the treatment of a number of blood malignancies came from the understanding and targeting of mechanisms of cell survival. Indeed, Venetoclax, an apoptosis-inducing agent, has been approved by the Food and Drug Administration for the treatment of older AML patients. However, even in AML, resistance ensues after prolonged Venetoclax treatment. Significant efforts have focused on understanding the drug resistance against apoptosis-inducing agents. Our previous studies highlight the importance of mitochondrial structure and function in the acquisition of drug resistance in AML. In this study, we attempt to identify mechanisms of resistance from Venetoclax treatment in MDS patients from the aspect of mitochondrial adaptation and propose therapeutic options to circumvent drug resistance by introducing a novel compound that strongly synergizes with apoptosis-inducing agents. We believe such combinatorial treatments can improve patient lives and even ensure long periods of remission for MDS patients, at least the ones that fail to respond well to conventional therapeutic options.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210844
Entities
People
- Iannis Aifantis
Organizations
- Grossman School of Medicine
- United States Army