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OHSU # 3286 — CD74 as a biomarker and therapeutic target for familial platelet (FPD) disorder

Summary
Research at OHSU has identified the CD74 signaling cascade as a potential therapeutic target and diagnostic biomarker for RUNX1-mutated familial platelet disorder (FPD), which is a premalignant condition for acute myeloid leukemia. 

Technology Overview
Current estimates suggest as many as 18,000 people may be living with RUNX1-FPD in the United States, and these patients are at an increased risk for the development of blood and bone marrow cancers. Roughly 35-40% of FPD patients go on to develop acute myeloid leukemia at an average age of 33 years.  As such, diagnosis of FPD as a premalignant condition and subsequent monitoring could improve patient outcomes and survival.  Currently, the diagnosis of FPD is based solely on next generation sequencing of RUNX1, but even after diagnosis there is no preventive treatment available for these patients

Researchers at OHSU have uncovered a novel inflammatory pathway activated in FPD patients that has potential as both a diagnostic and therapeutic target.  Analysis of hematopoietic stem and progenitor cells identified a predisposition towards myeloid cell differentiation and high levels of activation of the inflammatory CD74/PI3K/mTOR/JAK2 pathway.  In vivo data from Runx1R188Q/+ -mutated mice demonstrates that inhibition of the CD74 signaling cascade reverses the myeloid cell differentiation defect, and as such could be a causal contributor to the development of leukemia in FPD patients.

Research is ongoing to develop a flow-based diagnostic assays for FPD based on CD74 receptor levels within CD34+ mononuclear cells and an immunohistochemistry-based assay of bone marrow biopsy. Additionally, research to determine whether blockade of CD74 could potentially serve as a novel therapeutic target for preventing acute myeloid leukemia in patients with FPD is underway.  This current research program could address an unmet need for better diagnostic and treatment methods for FPD patients, to ultimately reduce and/or mitigate the risk of leukemia.

Licensing Opportunity
This technology is available for licensing.

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