New Genetic Testing Offers Hope for Chronic Blood Diseases: Rare Cancers Share a Genetic Mutation

Share Article

Chronic myeloproliferative neoplasms, or MPNs, are a group of incurable blood cancers that affect up to 100,000 Americans and, until fairly recently, were a mystery to scientists. What caused MPNs? And why were some people more susceptible than others? The question is being answered, at least in part, right now. Researchers believe that identifying genetic mutations holds some of the answers for earlier diagnosis and the development of better treatments.

Chronic myeloproliferative neoplasms, or MPNs, are a group of incurable blood cancers that affect up to 100,000 Americans and, until fairly recently, were a mystery to scientists. Doctors had long since determined that these deadly diseases caused the body to produce excessive blood cells, but were in the dark about their origins: What caused MPNs? And why were some people more susceptible than others?

The question is being answered, at least in part, right now. Researchers believe that identifying genetic mutations holds some of the answers for earlier diagnosis and the development of better treatments.

The first step came a few years ago, when researchers found the first genetic link to MPNs: Mutations of a protein called Janus kinase 2 (or JAK2 for short) can lead to activation of what’s known as the JAK-STAT pathway, a signaling mechanism for various proteins and other substances that control cellular communication and growth. When activated, the JAK-STAT pathway stimulates cell proliferation and other processes (and, when damaged, can lead to cancer). A single acquired mutation in JAK2 was identified in more than half of the chronic MPD patients tested, leading the researchers to hypothesize that MPD cancers are directly tied to mutations in JAK2.

Since then, other studies have ID’d several other common genetic denominators in patients with MPNs. For example, we now know that mutations in a genetic sequence known as MPLW515 are also linked to the JAK-STAT pathway — and the development of an MPN. And, just this year, researchers have discovered a connection to mutations in a gene known as TET2.

“The discovery of these mutations has completely modified the understanding, diagnosis, and management of MPNs,” says Dr. Shashi Pawar, director of genetics at Acupath Laboratories, Inc., a New York pathology lab. In fact, she notes that the World Health Organization recently changed its diagnostic criteria for MPNs to include JAK2 and MPL mutations. “As we continue to identify other genetic factors, we can develop better diagnostic tools —and drugs — to help more patients, more quickly.”

“Chronic MPD is a hematomalignancy, or cancer of the blood, that’s characterized by increases in one or more of the elements of the blood — like red blood cells and platelets — plus a tendency to develop excessive cells in the bone marrow,” Dr. Pawar explains. “We know that thrombopoietin (TPO) and the TPO receptor (MPL) are the key to platelet regulation, and we’ve shown that people with MPNs typically have a shortfall in MPL. Thus, we know that testing for MPL as well as JAK2 can help us diagnose and treat MPNs. And since we already have JAK2 mutation test available to our clients, it makes sense to have a test to detect mutation in MPL as well.”

And, as time goes by and more connections are made, the discovery of genes and genetic factors that are associated with MPNs will help researchers develop more accurate tests and treatments.

About MPNs
The three types of MPNs, polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), are what experts call clonal hematopoietic stem-cell disorders, which are caused by an acquired, rather than inborn, mutation in blood cells — an injury to the DNA of a single cell in the bone marrow, where blood cells are formed, that causes it to become malignant and multiply uncontrollably (and interfere with the body's production of healthy blood cells). IN PV, the marrow produces too many red blood cells, in ET it produces excessive platelets, and in PMF, the marrow develops scar-like lesions because of an overabundance of white cells and platelets and an inadequate supply of red blood cells.

About Dr. Pawar: Shashi Pawar, Ph.D, FACMG, is director of genetics at Acupath, Inc. With more than 20 years of varied experience in molecular genetics and molecular pathology, Dr. Pawar is board-certified in both clinical cytogenetics and clinical molecular genetics. Prior to joining Acupath, Dr. Pawar was technical director for Genova Diagnostics. She has been named a diplomat of the American Society of Human Genetics and a member of the association of Molecular Pathology. In addition, she has been published in the Journal of Biological Chemisty and the Proceedings of National Academy of Sciences, among others. She earned her Ph.D. in biochemistry at the City University of New York.

About Acupath Laboratories: Acupath Laboratories, Inc. is a Plainview, New York, specialty medical lab engaged in leading-edge molecular and cytogenetic analysis. http://www.acupath.com

# # #

Share article on social media or email:

View article via:

Pdf Print

Contact Author

MELISSA CHEFEC

203-968-6625
Email >