Note: This review is based upon a presentation at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10 in New Orleans, Louisiana.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report.
Abstract # 802
Bogdan Dumitriu, M.D., Xingmin Feng, Ph.D., Yasutaka Ueda, M.D., Ph.D., Sachiko Kajigaya, Ph.D., Danielle Townsley, M.D., Jun Zsu, Ph.D., Yoshi Wakabayashi, Ph.D., Yanqin Yang, M.S., Delong Liu, Ph.D., and Neal S. Young, M.D.
Some patients with aplastic anemia have very short telomeres. Telomeres are located at the ends of chromosomes and help keep chromosomes stable. As people age, their telomeres become shorter. Patients who have aplastic anemia and very short telomeres at diagnosis have a higher risk of progression to myelodysplastic syndromes (MDS).
Researchers from the National Heart, Lung, and Blood Institute at the National Institutes of Health compared mutations (changes) in genes and unstable chromosomes (measured by telomere length) in 43 patients with aplastic anemia. Aplastic anemia had progressed to monosomy 7 in 13 of these patients. Monosomy 7, a type of MDS, involves the loss of one of two number 7 chromosomes.
- The telomeres in cells from patients who developed MDS began getting shorter at a rapid rate as soon as these patients were diagnosed and even before they developed monosomy 7.
- In patients with stable aplastic anemia (who did not develop MDS), telomeres did not become shorter more quickly than in healthy people.
- Two patients who developed monosomy 7 had acquired mutations (changes in their genes that developed after birth) in the DNMT3A gene. One of these patients also had mutations in DOTL1, ASXL1, SETBP1, and STAT3.
- None of the other 11 patients with monosomy 7 had mutations in any of the genes tested.
- Telomeres became shorter at an early stage in the development of cancer in these patients.
- Identifying very short telomeres before the development of acquired genetic mutations might improve the management of patients with aplastic anemia that could progress to MDS.
- Drugs to increase the activity of telomerase, an enzyme that maintains telomere length, might reduce the risk of cancer in patients with aplastic anemia.