NEW YORK (Reuters Health) - Mutations in the gene for telomerase reverse transcriptase (TERT) seem to play a role in some cases of acquired aplastic anemia, according to a new report.
With acquired aplastic anemia, cytotoxic T cells typically attack the bone marrow, destroying hematopoietic cells and leaving fatty tissue behind.
In studying aplastic anemia and other autoimmune diseases, “the focus has been entirely on the immune side,” senior author Dr. Neal S. Young, from the National Institutes of Health in Bethesda, Maryland, told Reuters Health. “As far as I know, this is really the first example in which the target organ itself has a genetic problem.”
He explained that the TERT mutations seem to shorten the length of telomeres, the structural elements that protect chromosomes from damage. Ultimately, this leads to cell senescence and death. In the bone marrow, such mutations could reduce the number of stem cells present, increasing the odds that clinical disease will occur in the event of an immune attack.
In a healthy person, “an immune attack on the bone marrow might reduce stem cells by 20%, which is not a big deal because you’ll grow them back,” Dr. Young noted. “In contrast, if you start with just 10% of the normal number of stem cells, that’s a big loss.”
The findings are based on a study of 124 patients with apparently acquired aplastic anemia and 282 control subjects. The researchers looked for mutations in TERT and in three other telomerase-related genes -- DKC1, NHP2, and NOP10.
Five different TERT mutations were identified in seven unrelated patients. Leukocytes from these patients showed low telomerase enzymatic activity and short telomeres. Leukocytes from family members carrying the mutations had the same features, but no hematologic abnormality was seen.
No mutations in DKC1, NHP2, or NOP10 were identified in the study group, the investigators report in the April 7th issue of The New England Journal of Medicine.
Dr. Young said further research will be needed to determine the percentage of acquired aplastic anemia cases involving TERT mutations.
In a related editorial, Dr. Willem E. Fibbe, from Leiden University Medical Center in the Netherlands, comments that the “identification of TERT mutations in aplastic anemia is an important step toward defining the spectrum of aplastic anemia. This new finding may help in the development of individualized therapy at an early stage of the disease.”
N Engl J Med 2005;1413-1424,1481-1483.
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