Assessing Clonal Fitness and Mechanisms of Clonal Evolution in FPD-MN

Institution: 

Memorial Sloan-Kettering Cancer Center

Researcher(s): 

Wenbin Xiao, MD/PhD

Grant Type: 

RUNX1 Early Career Investigator Grants

Year Awarded: 

2020

Type of Childhood Cancer: 

Leukemia, Acute Myeloid Leukemia (AML), Predisposition

Germline RUNX1 mutations are commonly observed in familial platelet disorders (FPD); FPD patients have a high rate of transformation to myeloid neoplasms (FPD-MN). The molecular pathogenesis of FPD-MN remains elusive.

Project Goal
The research proposed here will use novel mouse models to identify contexts in which oncogenic RUNX1 mutations are necessary for disease progression and maintenance. These studies will provide insights into mechanisms of clonal fitness and leukemic transformation in FPD, which can help identify FPD patients at highest risk of transformation and inform the development of novel therapeutic approaches to prevent/intercept disease progression.

Project Update 2024:

With the support from ALSF we have developed and characterized a novel mouse model of FPD-AML, which allows us to investigate the disease progression of FPD. We identified potential therapeutic vulnerabilities in FPD-AML, which will be validated in future studies.