Childhood Cancer

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Characterizing Inflammatory Phenotypes Associated with RUNX1 Deficiency

Dana-Farber Cancer Institute
Waihay Wong, MD/PhD
Grant Type: 
RUNX1 Early Career Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Leukemia, Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL)
Project Description: 

Runt-related transcription factor 1 (RUNX1) plays key regulatory roles in blood cell development and disease. Inherited mutations in RUNX1 gene results in familial platelet disorder with predisposition to AML (FPD/AML), a condition characterized by easy bleeding or bruising as a result of low platelet levels and an increased risk of acute myeloid leukemia or other hematologic cancers in middle age. Somatic mutations in RUNX1 gene can also be acquired later in life, giving rise to blood cancers such as myelodysplastic syndrome and acute myeloid leukemia. Both inherited and somatically acquired RUNX1 mutations lead to a loss of RUNX1 function in blood cells. However, the mechanism by which RUNX1 loss results in hematopoietic disease remains unclear.

Project Goals

This project is focused on whether RUNX1 mutations cause increased inflammation in the bone marrow and other organs, and whether the heightened immune response contributes to inflammatory conditions and disease progression in individuals lacking RUNX1. We will evaluate the precise molecular mechanisms by which RUNX1 regulates inflammation in myeloid white blood cells and assess the ability of inhibitors of inflammation to suppress the pro-inflammatory features of RUNX1-mutated myeloid white blood cells. We will use genetic mouse models to investigate the link between RUNX1 loss and inflammatory conditions associated with FPD/AML. We will study the role of inflammation in promoting disease progression in mice bearing RUNX1-mutated hematopoietic cells and determine whether inhibitors of inflammation can slow the course of disease in mice, with the goal of identifying new strategies for early intervention of disease progression in the setting of RUNX1 deficiency.

Co-funded by: 
The RUNX1 Research Program