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UVA Unlocks Secrets of Mysterious Disappearing Leukemia
  • USA - English


News provided by

University of Virginia Health System

Feb 10, 2014, 12:45 ET

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CHARLOTTESVILLE, VA (PRWEB) February 10, 2014 -- Research at the University of Virginia School of Medicine has shed light on a mysterious form of leukemia that can appear and then disappear in children with Down syndrome. The findings may have important implications for other forms of leukemia and other diseases, possibly leading to new treatments, and could one day help people with problems related to platelet deficiencies as well.

These leukemias in Down syndrome aren’t that common, but this finding has implications for other leukemias.

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Throttled Open
The researchers have linked a mutation causing Down syndrome-associated leukemias to specific developmental abnormalities in cells that produce platelets, megakaryocytes. Essentially, this mutation is interfering with an enzyme, Calpain 2, that acts as an initial trigger for a chain of reactions that determines size and shape of megakaryocytes. This interference causes the normal process of cellular enlargement and platelet production to get hung up. “It’s like there’s a long pipeline and there’s a clog,” explained Adam N. Goldfarb, MD, of the Department of Pathology. “We think it’s this pipeline that’s getting clogged in this disease and other diseases.”

Leukemia cells with the mutation display a critical deficiency of Calpain 2, and the enzyme’s absence leaves them stuck in an early stage of development, contributing to the development of Down syndrome-associated leukemias, Goldfarb said. And that could be the case in other forms of leukemia as well. “These leukemias in Down syndrome aren’t that common, but this finding has implications for other leukemias in that it lets us understand basic growth and development patterns,” Goldfarb said.

Restoring Calpain 2 expression in affected cells, the researchers found, fixed the problem and allowed the normal megakaryocyte developmental process to resume. As such, the researchers hypothesize that calpain deficiency could be a key defect in Down syndrome-associated leukemias, opening up a new target for developing more effective treatments. And, eventually, it could lead to ways for doctors to mimic the natural process that allows a subset of Down syndrome-associated leukemias to disappear spontaneously.

Big Picture
The new research is also notable for the understanding it provides about the development and growth of megakaryocytes, the large cells that produce platelets. Megakaryocytes recover slowly after chemotherapy, and they’re easily destroyed, so it’s important to understand how they develop and find ways to control their replication and growth.

Megakaryocytes differ in size in neonatal infants versus older individuals, and they behave differently as well. By understanding why, scientists may one day be able to toggle them between the forms seen in neonates – when they’re smaller but proliferate more quickly – and in adults, when they’re more effective at platelet production. That could prove invaluable in developing new treatments for low platelet counts.

Published Online
The findings have been published online by the journal Developmental Cell and will appear in an upcoming print edition. The article was authored by Kamaleldin E. Elagib, Jeremy D. Rubinstein, Lorrie L. Delehanty and Valerie S. Ngoh, all of UVA; Peter A. Greer of Queen’s University in Ontario; Shuran Li and Jae K. Lee, of UVA; Zhe Li and Stuart H. Orkin, of Harvard; and Ivailo S. Mihaylov and Goldfarb, of UVA.

Goldfarb made particular mention of the contributions of Elagib, the first author on the paper, saying he “gets a huge amount of credit for persistence” in pursuing the research.

FOR REPORTERS: Goldfarb is available for interviews. To arrange an interview, contact Josh Barney at 434.906.8864 or jdb9a(at)virginia(dot)edu.

####

Josh Barney, University of Virginia Health System, http://www.uvahealth.com, +1 434.906.8864, [email protected]

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