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Drug Screen for FPD/AML Therapeutics

Children’s Hospital of Philadelphia
Mortimer Poncz, MD
Grant Type: 
RARE Grant Program (Research Accelerating RUNX1 Exploration)
Year Awarded: 
Type of Childhood Cancer: 
Acute Myeloid Leukemia (AML)
Project Description: 

Co-Investigators: Deborah French, PhD & Paul Gadue, PhD


Familial platelet disorder associated with acute myeloid leukemia (FPD/AML) occurs when an individual has half the normal levels of a protein called RUNX1. Affected individuals have both bleeding, due to platelets being low and not working well, and an increased risk of developing AML. We propose to enhance the level of RUNX1 to correct the platelet problem and we expect that correcting the platelet problem will also correct the risk of developing AML. Our group specializes in studies on how to make platelets from megakaryocytes. We have already identified one drug called RepSox that can correct many of the megakaryocyte defects seen in FPD/AML cells. 

Project Goal

We now propose to continue studies with RepSox and also screen drugs for other compounds that correct FPD/AML megakaryocytes at acceptable doses. We will also test these drugs in RUNX1-deficient mice. We will adjust candidate drugs to the lowest level that corrects the platelet counts in these mice. Our longer-term goal is to test whether that dose protects the mice from getting leukemia. We envision applying this strategy to affected individuals who will take the drug at the lowest dose that corrects their platelet count with the expectation that the dose will also protect the individual from AML with fewer side-effects. We believe that the proposed strategy offers a short-track for drug identification that both reduces the risk of bleeding and of developing AML.