Transcriptional Effectors of Activated RAS Signaling in Juvenile Myelomonocytic Leukemia

Background:

Juvenile myelomonocytic leukemia (JMML) is an aggressive blood cancer of young children, typically affecting those less than 4 years of age. The only current curative treatment is bone marrow transplantation. Yet, despite this very aggressive therapy about 50% of children still ultimately die from their disease. Thus, more effective and less toxic treatments are urgently needed.

Project Goal:

Our preliminary studies show that RUNX1, a protein that normally turns on white blood cell growth promoting genes, is aberrantly activated in JMML. Importantly, a drug that inhibits RUNX1 activity is available and has been used in humans with little toxicity.  We hypothesize that RUNX1 is a new therapeutic target in JMML and that RUNX1 inhibitors will be beneficial in the treatment of this childhood cancer. This proposal tests these hypotheses using mouse models of JMML and data from human patient JMML samples. Positive results from this study could be rapidly translated into clinical trials given the prior use of the RUNX1 inhibitory compound in humans.