Damon Runyon Researchers

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Sakiko Suzuki, MD

Despite many recent advances, today’s treatment of leukemia still relies on medications that have very toxic side effects and can cause death. Therefore, it is crucial to search for new types of therapies that directly target leukemia without harming the normal cells of the body. A gene called MPL encodes a protein found to be important for the growth and survival of a significant proportion of Acute Myeloid Leukemias (AMLs) and other blood diseases including Essential Thrombocythemia (ET), a malignancy affecting the platelet-producing cells of the bone marrow. Sakiko has been focusing on the function of a truncated variant of MPL produced by splicing out a section of the MPL RNA message used to make the protein. This variant, MPL-TR, opposes the function of MPL in cells; she believes that increasing MPL-TR in leukemia cells will suppress their growth. Anti-sense oligonucleotides (AONs) are very short segments of RNA or DNA that can be constructed to bind specifically to RNA messages in the cell, so no other genes are affected. By targeting AONs to the regions in MPL RNA important for splicing, she proposes that leukemia cells will make more MPL-TR, thus inhibiting their growth and survival. She will test a series of AONs targeting human MPL splicing, designed to enhance levels of MPL-TR. These experiments will provide the foundation for establishing a clinical trial with the novel, targeted AON. The principles founded by this project would also be broadly applicable for targeting splicing in other genes essential for multiple forms of leukemia and lymphoma.

Project title: "AON-directed alternative splicing as a novel therapy for leukemia"
Institution: University of Massachusetts Medical School
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Michelle A. Kelliher, PhD, and Peter E. Newburger, MD
Cancer Type: Blood, Other Cancer
Research Area: Experimental Therapeutics