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UAMS reports myeloma finding 

Hope for targeted treatments

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UAMS Medical Center

UAMS Study Finds Genetic Subtypes of Myeloma,Hope for Targeted Treatments

LITTLE ROCK – A genetic analysis of more than 400 patients with multiple myeloma, a cancer of the bone marrow, identified seven subtypes of the disease that had a bearing on a patient’s prognosis and offered the potential for targeted treatments, reported a team of researchers from the University of Arkansas for Medical Sciences (UAMS) in the September issue of the journal Blood.

The researchers from the Myeloma Institute of Research and Therapy (MIRT) in the Arkansas Cancer Research Center (ACRC) at UAMS used gene expression profiling to analyze bone marrow plasma cells from 414 newly diagnosed myeloma patients. Of the seven genetic disease subtypes identified, four were associated with better patient outcomes following high-dose chemotherapy and a stem cell transplantation.

An article on the study, “The molecular classification of multiple myeloma,” is published in the Sept. 15, 2006, issue of Blood, the journal of the American Society of Hematology. The article is available online at http://www.bloodjournal.org/.

“These results are likely to have a profound influence on the diagnosis, prognosis and treatment of multiple myeloma,” said John D. Shaughnessy Jr., Ph.D., director of the Lambert Laboratory in the MIRT where the research took place, and a professor in the UAMS College of Medicine. “While on the surface most myelomas look alike, the power of modern molecular techniques has allowed us to identify the specific genetic switches that are altered in each disease subtype and these insights may offer entry points for new tailored therapeutic options.”

The study noted that although high-dose therapy improved the prognosis for patients with multiple myeloma, individual patients’ survival remains variable and unable to be accurately predicted. The researchers said the relationship between the disease subtypes and survival rates should lead to better risk stratification.

Fenghuang Zhan, M.D., Ph.D., an assistant professor in the UAMS College of Medicine is the lead author of the article. Together with Shaughnessy, other authors of the article from UAMS were:

Yongsheng Huang, computer scientist research associate, MIRT
Simona Colla, Ph.D., post doctoral fellow, MIRT
James P. Stewart, Ph.D., post doctoral fellow, MIRT
Inchiro Hanamura, M.D., Ph.D., post doctoral fellow, MIRT
Sushil Gupta, Ph.D., post doctoral fellow, MIRT
Joshua Epstein, D.Sc., professor of medicine
Shmuel Yaccoby, Ph.D., associate professor of medicine and physiology
Jeffrey Sawyer, Ph.D., professor of pathology
Elias Anaissie, M.D., professor of medicine
Klaus Hollmig, M.D., assistant professor of medicine
Mauricio Pineda-Roman, M.D., assistant professor of medicine
Guido Tricot, M.D., Ph.D., professor of medicine and pathology
Frits van Rhee, M.D., Ph.D., associate professor of medicine
Ronald Walker, M.D., assistant professor of radiology
Maurizio Zangari, M.D., associate professor of medicine
Bart Barlogie, M.D., Ph.D., director of the MIRT and a professor of medicine and pathology
The MIRT continues to be at the forefront of myeloma research. In the Sept. 1 issue of the same journal, Shaughnessy’s group reported on the identification of a critical genetic lesion that contributes to disease progression and drug resistance.

Shaughnessy was one of three lead authors in a study published in the April issue of the journal Cancer Cell that described a high-resolution map of the DNA gains and losses in multiple myeloma and the genes affected by these genetic anomalies.

Multiple myeloma is a cancer of the plasma cells – white blood cells in the bone marrow that produce antibodies. It is the second most common cancer of the blood and is almost always associated with debilitating bone destruction.

Researchers at MIRT led by Shaughnessy published a report in the Dec. 25, 2003, issue of the New England Journal of Medicine describing the molecular mechanism by which myeloma cells cause bone destruction. The MIRT program is now developing new therapies to combat this serious disease complication.

Therapy at the MIRT has led to a more than doubling of the median survival rate of a myeloma patient upon diagnosis from three years to seven years and beyond.

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