Exploring the Impact of Base Deaminase Deregulation on Precancer Evolution
Description: PROJECT NARRATIVE In 295,000 individuals in the US who are living with myeloproliferative neoplasms (MPNs), progression to therapy resistant secondary acute myeloid leukemia (sAML) remains a major cause of morbidity and mortality as well as growing healthcare economic burden thereby underscoring the pressing unmet medical need for predicting and preventing MPN progression. Recently, we discovered that inflammatory cytokine-induced activation of APOBEC3C and ADAR1p150 base deaminases fuels hematopoietic stem and progenitor cell (HSPC) proliferation during leukemic transformation of MPNs. Thus, the overarching goal of this project is to elucidate the APOBEC3C-mediated DNA and ADAR1p150-mediated RNA editing mechanisms governing MPN HSPC reprogramming into long-lived, self-renewing leukemia stem cells (LSC) with the ultimate aim of informing the development of strategies that predict and prevent sAML transformation.
Funder: National Institutes of Health
Amount: $445,000
Funding type: research
Funder scheme: R01
Start date: 2024-12-01
End date: 2029-11-30
Investigator: LUDMIL B ALEXANDROV
Institution: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Funded outputs count: 10
Funder award ID: 1r01ca296974-01
OpenAlex ID: G9000887757