New project to focus on role of Myc oncoproteins in B-cell lymphoma

The Scripps Research investigators hope project will reveal suitable drug targets

The National Institutes of Health has awarded The Scripps Research Institute $2 million to study the role of a pathway in the development and maintenance of B-cell lymphoma, a type of cancer that begins in immune system and turns normal disease fighting cells into cancers. The disease affects immune cells known as lymphocytes, which are part of our white blood cells.

John Cleveland, PhD, chair of the Department of Cancer Biology on the Scripps Florida campus, will be the principal investigator for the new five-year study.

B-cell lymphomas tend to occur in older patients and in those people whose immune system has been compromised. It is one of the most common blood cancers in the United States and kills about 20,000 Americans each year.

The new project will focus on the role of Myc oncoproteins-the products of Myc oncogenes-which are activated in over half of all human tumor types. Myc oncoproteins accelerate the rate of cell growth, which increases the risk of acquiring additional mutations that allow a premalignant cell to develop into a full-blown tumor. In this project, the Cleveland lab will investigate the role of a pathway that controls the destruction of a class of messenger RNAs (mRNAs) that encode proteins that regulate the development and maintenance of tumors.

"This grant allows us to focus on a new pathway that is controlled by Myc that we think is suitable to target for the development of new anti-cancer drugs," said Cleveland, who has led numerous studies shedding light on this oncogene. "We are very hopeful that learning more about this process will open the door for the development of new treatments."

Specifically, the new project aims to define the mechanisms by which Myc controls the expression and function of Tristetraprolin or TTP, a mRNA-binding protein that normally controls the destruction of a subset of important mRNAs. Importantly, Research Associate Robert Rounbehler, PhD, and other colleagues in the Cleveland lab have shown that TTP functions as a tumor suppressor that impairs the development and maintenance of B lymphoma. Their findings indicating that agents that regulate TTP or affect its key mRNA targets hold great promise as anti-cancer agents.