Telomere elongation and clinical response to androgen treatment in a patient with aplastic anemia and a heterozygous hTERT gene mutation

Telomere length (TL) both reflects and limits the replicative life span of normal somatic cells. As a consequence, critically shortened telomeres are associated with a variety of disease states. Telomere attrition can be counteracted by a nucleoprotein complex containing telomerase. Mutations in sub...

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Bibliographic Details
Published in:Annals of hematology 2012-07, Vol.91 (7), p.1115-1120
Main Authors: Ziegler, Patrick, Schrezenmeier, Hubert, Akkad, Jamil, Brassat, Ute, Vankann, Lucia, Panse, Jens, Wilop, Stefan, Balabanov, Stefan, Schwarz, Klaus, Martens, Uwe M., Brümmendorf, Tim H.
Format: Article
Language:English
Subjects:
Androgens
Androgens - therapeutic use
Anemia, Aplastic - diagnosis
Anemia, Aplastic - drug therapy
Anemia, Aplastic - genetics
Anemia, Aplastic - metabolism
Aplastic anemia
Bone marrow
Codons
Hematology
Heterozygote
Humans
Male
Medicine & Public Health
Middle Aged
Mutation
Nucleoproteins
Oncology
Original Article
Peripheral blood
Somatic cells
Stem cells
Telomerase - genetics
telomerase reverse transcriptase
Telomere - metabolism
Telomeres
Transfusion
Treatment Outcome
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Summary:Telomere length (TL) both reflects and limits the replicative life span of normal somatic cells. As a consequence, critically shortened telomeres are associated with a variety of disease states. Telomere attrition can be counteracted by a nucleoprotein complex containing telomerase. Mutations in subunits of telomerase, telomerase-binding proteins as well as in members of the shelterin complex have been described both in inherited and acquired bone marrow failure syndromes. Here, we report on a patient with acquired aplastic anemia and a nonsynonymous variation of codon 1062 of the h TERT gene (p.Ala1062Thr) whose substantial and maintained hematologic response to long-term androgen treatment (including complete transfusion independence) was paralleled by a significant and continued increase in TL in multilineage peripheral blood cells. To our knowledge, this represents the first case of sustained telomere elongation in hematopoietic stem cells induced by a pharmacological approach in vivo (141 words).
ISSN:0939-5555
1432-0584
DOI:10.1007/s00277-012-1454-x