title: Telomere elongation and clinical response to androgen treatment in a patient with aplastic anemia and a heterozygous hTERT gene mutation.
abstract: 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 hTERT 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).
authors.affiliation: Department of Oncology, Hematology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ziegler
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Jamil
authors.initials: J
authors.lastname: Akkad
authors.forename: Ute
authors.initials: U
authors.lastname: Brassat
authors.forename: Lucia
authors.initials: L
authors.lastname: Vankann
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilop
authors.forename: Stefan
authors.initials: S
authors.lastname: Balabanov
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Uwe M
authors.initials: UM
authors.lastname: Martens
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
mesh_terms: D000728:Androgens / Q000627:therapeutic use*; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000728:Androgens; C509186:TERT protein, human; D019098:Telomerase