12:37am Monday 13 July 2020

Researcher discovers new target for leukemia treatment

In a paper published Feb. 11 in Leukemia, a Nature journal, a UT Health Science Center San Antonio research team has pinpointed a protein that could play a key, previously unknown role in the development of AML — promising new information in the quest to treat and cure leukemias.

AML begins when blood cells differentiate
AML starts at the point when cells mature into different kinds of blood cells. In AML, the cancerous cells grow and proliferate in an abnormal way, and they fail to develop, or differentiate, into normal functioning white blood cells. Also, high levels of a protein called WTAP contribute to abnormal cell behavior, observed Sanjay Bansal, Ph.D., a researcher at the Greehey Children’s Cancer Research Center, part of the UT Health Science Center.

The tumors on the left are from acute myeloid leukemia (AML) cells in which the protein WTAP was present, contributing to abnormal cell growth. On the right are AML tumors without WTAP. Knocking out WTAP greatly suppressed proliferation of AML cells. clear graphic
The tumors on the left are from acute myeloid leukemia (AML) cells in which the protein WTAP was present, contributing to abnormal cell growth. On the right are AML tumors without WTAP. Knocking out WTAP greatly suppressed proliferation of AML cells. clear graphic

 


Removing WTAP promoted normal cell development
Dr. Bansal and his team, working with leukemia cells, used a laboratory technique to “knock down,” or remove, WTAP expression in AML cells. What resulted was, in the research world, a resounding success.

“Knocking down this protein, WTAP, greatly suppressed proliferation and induced differentiation,” said Hima Bansal, Ph.D., senior research associate at the Health Science Center and lead author of the paper. “It took care of both problems.”

Hsp90 controls expression of WTAP
The researchers, however, needed to understand how WTAP levels get so high in AML in the first place. The researchers turned to another protein called Hsp90, a so-called “molecular chaperone” that helps stabilize more than 200 other proteins, known as Hsp90 “clients.”

“When we suppressed Hsp90, we reduced WTAP,” Dr. Bansal said. “So we have discovered two things: WTAP’s role in AML and the mechanism underlying its overexpression.”

Many of Hsp90’s other client proteins are known targets in oncology, and “WTAP joins the list,” Dr. Bansal said.

This discovery could open the door to more effective therapies for children and adults with newly diagnosed AML or for patients who have failed currently available treatments.

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The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the elite academic cancer centers in the country to be named a National Cancer Institute (NCI)-designated Cancer Center, and is one of only four in Texas. A leader in developing new drugs to treat cancer, the CTRC Institute for Drug Development (IDD) conducts one of the largest oncology Phase I clinical drug programs in the world, and participates in development of cancer drugs approved by the U.S. Food & Drug Administration. For more information, visit www.ctrc.net.

Contact: Elizabeth Allen, 210-450-2020


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