AUG 04, 2015 11:22 AM PDT

Decoding Chromosome 21

A gene on a chromosome linked with Down syndrome also has implications for developing childhood leukemia, according to researchers at Northwestern University School of Medicine. Their work, published in the Journal of Experimental Medicine and reported in Bioscience Technology, sheds light on how the DYRK1A gene functions (http://www.biosciencetechnology.com/news/2015/08/uncovering-genetic-factors-leukemia?et_cid=4709958&et_rid=45505806&type=cta).
Northwestern University researchers pinpoint the reason children with Down syndrome are more likely to contract leukemia.
According to the American Cancer Society, children with Down syndrome have an extra (third) copy of chromosome 21 (also called trisomy). These children are 20 times more likely to develop either acute lymphocytic leukemia or acute myeloid leukemia than are other children, with an overall risk of about 2 to 3 percent. Down syndrome has also been linked with transient leukemia, a leukemia-like condition within the first month of life, which often resolves on its own without treatment (http://www.cancer.org/cancer/leukemiainchildren/detailedguide/childhood-leukemia-risk-factors).

Because that chromosome is important for research in the genetic basis of the cancer, it is a "major goal...to identify the specific gene - or genes - on chromosome 21 responsible for the increased incidence of leukemia in this population," said study senior author John Crispino, Ph.D., Robert I. Lurie, M.D., and Lora S. Lurie Professor in Medicine-Hematology/Oncology and Biochemistry and Molecular Genetics. Supported by a National Institutes of Health grant, the Samuel Waxman Cancer Research Foundation, the Leukemia and Lymphoma Society, the Rally Foundation and the Bear Necessities Foundation, Crispino's laboratory conducted a study to determine how the leukemia-promoting DYRK1A gene works in cells.

Crispino and his colleagues previously discovered that a gene on chromosome 21 called DYRK1A is linked with the development of leukemia. In the recent study they expanded on that research by evaluating the gene in depth. They specifically sought an understanding of how DYRK1A plays a part in blood cell production. The over-production of immature lymphocytes is a characteristic of acute lymphoblastic leukemia.

Crispino, along with first author Benjamin Thompson, M.D., Ph.D., a postdoctoral fellow, developed a mouse model that does not have DYRK1A in blood cells. The researchers noted that two types of white blood cells -- B and T lymphocytes -- were greatly hampered from developing without the gene. They also discovered evidence that DYRK1A is usually "responsible for regulating cell cycle progression in those lymphocytes." As they explained, "Because they have extra copies of chromosome 21, children with Down syndrome have more DYRK1A than usual."

Crispino concluded, "This finding is exciting to us because human B-cell acute lymphoblastic leukemia cases show increased levels of DYRK1A. The results suggest that DYRK1A may be a novel target for therapy in this form of leukemia."
About the Author
  • Ilene Schneider is the owner of Schneider the Writer, a firm that provides communications for health care, high technology and service enterprises. Her specialties include public relations, media relations, advertising, journalistic writing, editing, grant writing and corporate creativity consulting services. Prior to starting her own business in 1985, Ilene was editor of the Cleveland edition of TV Guide, associate editor of School Product News (Penton Publishing) and senior public relations representative at Beckman Instruments, Inc. She was profiled in a book, How to Open and Operate a Home-Based Writing Business and listed in Who's Who of American Women, Who's Who in Advertising and Who's Who in Media and Communications. She was the recipient of the Women in Communications, Inc. Clarion Award in advertising. A graduate of the University of Pennsylvania, Ilene and her family have lived in Irvine, California, since 1978.
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