Press Releases | 2012

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Moffitt Cancer Center Researchers Investigate Causes of Myelodysplastic Syndrome

Nov 15, 2012

TAMPA, Fla. (Nov. 15, 2012) – Researchers at Moffitt Cancer Center, along with research partners at Cleveland Clinic, Ronald Reagan UCLA Medical Center, Penn State Hershey Cancer Institute and Tianjin Medical University in China, have tied the development of one of the myelodysplastic syndromes (MDS) to a shortening of a cell component called telomeres..

The study can be seen on the website for Leukemia, a journal from the Nature Publishing Group.

Myelodysplastic syndromes, formally known as pre-leukemia, are disorders of the stem cells in the bone marrow. Blood production is disorderly and ineffective, and the number and quality of blood-forming cells reduce, further impairing blood production. Patients with MDS often develop severe anemia and require frequent blood transfusions. In most cases, the disease worsens and the patient develops low blood counts caused by progressive bone marrow failure. In about one third of patients with MDS, the disease transforms into acute myelogenous leukemia within months to a few years.

Seeking to understand more about the development of MDS, the research team investigated specialized cell structures called telomeres, which provide integrity to chromosomes during cell division and have been linked to biological aging when old cells cease to divide.

The mechanism for telomere loss in MDS has not been previously investigated. Through this study, researchers were able to define MDS as a “member of the telomere repair disorders” and related to the deregulation of the immune system’s T cells.

Mutations in telomere components have been identified in congenital and acquired aplastic anemia, which are epidemiologically and clinically linked to MDS. Telomerase is the  enzyme that adds DNA sequence repeats to DNA strands in the telomere regions at the ends of chromosomes. Telomerase allows for replacement of short bits of DNA (telomeres) when cells divide.

In MDS patients, telomere length is shortened by an unknown process that researchers said may be related to proliferative stress or ineffective telomeric repair.

Researchers compared telomerase gene expression in patients with MDS with telomerase expression in a healthy control group. They found that those with MDS had lower telomerase induction that may undermine telomere loss and promote changes in the immune system’s T cells.

“Our study revealed a mechanistic link between aplastic anemia, a characteristic of MDS, and other primary telomere repair disorders,” said study lead author P.K. Epling-Burnette, PharmD, Ph.D., senior member of Moffitt’s Immunology Program. “We found evidence of excessive activation-induced cell death in MDS T cells. A telomerase deficiency in naïve T cells hinders their regeneration, which may contribute to the accumulation of senescent cells (old cells unable to divide) in MDS.”

The researchers noted that defects in telomere repair have been reported in other inflammatory diseases, such as rheumatoid arthritis, and that the defect is linked to the repression of transcription, a process involved in cell signaling pathways.

“At this point, it is unclear which pathways are blocked in MDS. Opportunities to improve MDS diagnosis and design therapeutic interventions may be achieved from a better understanding of telomere abnormalities in T cells and in the stem cell compartment contributing to malignant transformation in MDS,” concluded Epling-Burnette.

Funding for this project was provided by the National Cancer Institute (R01 CA129952).

About Moffitt Cancer Center
Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s excellence in research, its contributions to clinical trials, prevention and cancer control. Since 1999, Moffitt has been listed in U.S. News & World Report as one of “America’s Best Hospitals” for cancer. With more than 4,200 employees, Moffitt has an economic impact on the state of nearly $2 billion. For more information, visit MOFFITT.org, and follow the Moffitt momentum on Facebook, twitter and YouTube.

Media release by Florida Science Communications  


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