Identification and Molecular Analysis of Pre-Myelofibrotic Stem Cells
Daniel ThomasMD PhD
The University of Adelaide
Project Term: July 1, 2022 - June 30, 2025
Myelofibrosis is a severe myeloproliferative neoplasm with no known cure.We have obtained unique insights into the underlying mechanisms responsible for the emergence of myelofibrosis and designed new approaches to selectively control it. By combining our mutation-specific isolation methods with single cell sequencing, we will identify myelofibrosis-initiating stem cell populations, demonstrate efficacy of stem cell targeting and enumerate residual normal stem cells to inform a Phase I/II trial.
Myelofibrosis is a poorly understood blood cancer that feels like having a chronic infection in which the patient’s bone marrow becomes stiff and fibrotic. There is currently no known cure and many cases eventually turn into acute leukemia. We have, for the first time, developed an antibody therapy that has great potential to remove the fibrosis-causing stem cells. We will use this as both a molecular tool to isolate and remove the bad stem cells that we believe are probably causing the disease. This work will be critical for a forthcoming Phase I/II clinical trial for younger patients with myelofibrosis who are progressing despite best treatment.