The RUNX1 Research Program is a new research and advocacy venture committed to funding world-class, innovative and cross-disciplinary cancer research to find a cure for those with the germline RUNX1 mutation, a familial platelet disorder with a predisposition to acute myeloid leukemia (FPD/AML). The program also aims to support, inform, educate and connect patients and healthcare providers in the RUNX1 community.

Frequently Asked Questions

What is RUNX1 FPD/AML?

RUNX1 FPD/AML is familial platelet disorder with a predisposition to acute myeloid leukemia. RUNX1 FPD/AML is a pre-leukemic disorder involving a likely autosomal dominant, inherited qualitative/quantitative defect of platelets associated with an approximately 50% lifetime risk of developing AML (an acute form of leukemia).

The underlying defect is caused by monoallelic mutations in RUNX1 that result in haploinsufficiency. In other words, in RUNX1 FPD/AML, one of the two copies of the RUNX1 gene is dysfunctional. RUNX1 is a transcription factor important for the formation of blood in the embryo from hemogenic endothelium. It is also important for the differentiation of many blood cell lineages including T lymphocytes and megakaryocytes. RUNX1 mutations in hematopoietic stem cells create a “pre-leukemic” stem cell that can ultimately acquire secondary mutations that convert it into a leukemia cell.

2017 RUNX1-LLS Grant Winners

The RUNX1 Research Project has a long-term partnership with the Leukemia and Lymphoma Society (LLS) to provide grants of $200,000 per year for three years for translational leukemia research related to the germline RUNX1 disorder. The hope of the grant program is to encourage and advance therapeutics, and to obtain a greater understanding of familial platelet disorders associated with RUNX1 mutations that lead to acute myelogenous leukemia (AML). Three grants up to $600,000 will be awarded, and this year we are pleased to announce that all three have been granted, to be funded starting in October 2017. We look forward to observing their progress over the coming years and will duly keep you informed. 

Dr. Guy Sauvageau, University of Montreal, Canada, ‘RUNX1 mutations that confer exquisite sensitivity to glucocorticoids’. Dr. Sauvageau discovered that a class of steroid hormones called glucocorticoids selectively inhibits the growth of acute myeloid leukemia (AML) cells containing RUNX1 mutations in cell culture. He plans to determine how glucocorticoids inhibit the growth of RUNX1 mutant AML cells, and to test the ability of glucocorticoids to inhibit AML in a mouse model. 

Dr. Benjamin Ebert, Harvard Medical School, USA, ‘Interaction of RUNX1 and the cohesin complex in megakaryocyte development and myeloid disease’. Dr. Ebert will study the cooperation between mutations in RUNX1 and in a gene encoding a member of the cohesin complex, STAG2. He plans to generate a mouse model for the combined RUNX1 and STAG2 mutations and study hematopoiesis and leukemia progression. He will also evaluate inhibitors of CDK8, a member of the transcriptional mediator complex, for their activity and mechanism of action in the context of RUNX1 and/or STAG2 mutations. 

Dr. Stephen Nimer, University of Miami - Miller School of Medicine, USA, ‘Epigenetic-modifying enzymes in FPD/AML’. Dr. Nimer will evaluate the ability of inhibitors or activators of epigenetic gene The RUNX1 Research Program 1 www.runx1.com Summer 2017 regulation to promote the differentiation, or inhibit the self-renewal, proliferation, and survival of RUNX1 mutant hematopoietic cells derived from cultures of human-induced pluripotent stem cells (iPSCs). He will also generate a mouse model with combined mutations in RUNX1 and in a gene called ASXL1, which have been found to co-occur in a subset of FPD/AML patients with AML, and test the activity of inhibitors or activators of epigenetic gene regulation in this model.