title: Bone marrow failure and the new telomere diseases: practice and research.
abstract: The telomeropathies are a newly described group of human diseases based on the genetics and molecular biology of the telomeres, the ends of chromosomes. Telomeres are repeated hexanucleotides and their associated proteins; the protect chromosomes from recognition  as damaged DNA, and their inevitable gradual loss with DNA replication is harmless as they are noncoding. However, when telomeres become critically short in a cell, senescence, apoptosis, or, rarely malignant transformation results. In individuals with mutations in genes involved in telomere  repair, especially the enzymatic telomerase complex, telomere attrition is accelerated. Severe deficiencies result in dyskeratosis congenita, a congenital aplastic anemia with associated mucocutaneous abnormalities. Mutations in TERT, the catalytic component, and TERC, the RNA template, can  behave as risk factors for the development of bone marrow failure, pulmonary fibrosis, and hepatic cirrhosis. Both penetrance and organ specificity are variable and not well understood. Chromosome instability is a result of critical shortening of telomeres and cancer. For example, short telomeres  are the major prognostic risk factor for clonal evolution to myelodysplasia and acute leukemia. Practically, hematologists need to recognize the multisystem presentation of telomere disease, implications for outcomes, and options for therapy.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA. youngns@nhlbi.nih.gov
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000235:genetics / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001855:Bone Marrow Diseases / Q000235:genetics / Q000473:pathology*; D043171:Chromosomal Instability; D019871:Dyskeratosis Congenita / Q000235:genetics / Q000473:pathology; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000473:pathology*
chemical_list: D019098:Telomerase