Androgen derivatives improve blood counts and elongate telomere length in adult cryptic dyskeratosis congenita.
MDS
androgens
bone marrow failure
dyskeratosis congenita
telomere
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
15
05
2020
accepted:
02
07
2020
pubmed:
4
8
2020
medline:
28
9
2021
entrez:
4
8
2020
Statut:
ppublish
Résumé
Dyskeratosis Congenita (DKC) is a systemic disorder caused by mutations resulting in impaired telomere maintenance. Clinical features include bone marrow failure and an increased risk of developing hematological malignancies. There are conflicting data whether androgen derivatives (AD) can elongate telomeres in vivo and whether AD treatment enhances the risk of gaining myelodysplastic syndrome-related mutations. Seven TERC or TERT-mutated DKC patients underwent AD treatment. All patients revealed hematological response. Telomere length of lymphocytes and granulocytes increased significantly and no MDS-related mutations were detected. Pending longer follow-up, treatment with AD seems to represent an efficient and safe therapy for DKC patients.
Substances chimiques
Androgens
0
telomerase RNA
0
RNA
63231-63-0
TERT protein, human
EC 2.7.7.49
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
669-673Informations de copyright
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Références
Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009;361:2353-65.
Ferreira MSV, Kirschner M, Halfmeyer I, Estrada N, Xicoy B, Isfort S, et al. Comparison of flow-FISH and MM-qPCR telomere length assessment techniques for the screening of telomeropathies. Ann N Y Acad Sci. 2020;1466(1):93-103.
Calado RT, Yewdell WT, Wilkerson KL, Regal JA, Kajigaya S, Stratakis CA, et al. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood. 2009;114:2236-43.
Bar C, Huber N, Beier F, Blasco MA. Therapeutic effect of androgen therapy in a mouse model of aplastic anemia produced by short telomeres. Haematologica. 2015;100:1267-74.
Ziegler P, Schrezenmeier H, Akkad J, Brassat U, Vankann L, Panse J, et al. Telomere elongation and clinical response to androgen treatment in a patient with aplastic anemia and a heterozygous hTERT gene mutation. Ann Hematol. 2012;91:1115-20.
Townsley DM, Dumitriu B, Liu D, Biancotto A, Weinstein B, Chen C, et al. Danazol treatment for telomere diseases. N Engl J Med. 2016;374:1922-31.
Khincha PP, Bertuch AA, Gadalla SM, Giri N, Alter BP, Savage SA. Similar telomere attrition rates in androgen-treated and untreated patients with dyskeratosis congenita. Blood Adv. 2018;2:1243-9.
Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow-up. Haematologica. 2018;103:30-9.
Kirschner M, Maurer A, Wlodarski MW, Ventura Ferreira MS, Bouillon A-S, Halfmeyer I, et al. Recurrent somatic mutations are rare in patients with cryptic dyskeratosis congenita. Leukemia. 2018;32:1762-7.
Wong JM, Kyasa MJ, Hutchins L, Collins K. Telomerase RNA deficiency in peripheral blood mononuclear cells in X-linked dyskeratosis congenita. Hum Genet. 2004;115:448-55.
Walne AJ, Vulliamy T, Kirwan M, Plagnol V, Dokal I. Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. Am J Hum Genet. 2013;92:448-53.
Brummendorf TH, Maciejewski JP, Mak J, Young NS, Lansdorp PM. Telomere length in leukocyte subpopulations of patients with aplastic anemia. Blood. 2001;97:895-900.
Brummendorf TH, Balabanov S. Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia. 2006;20:1706-16.
Stanley N, Olson TS, Babushok DV. Recent advances in understanding clonal haematopoiesis in aplastic anaemia. Br J Haematol. 2017;177:509-25.
Kulasekararaj AG, Jiang J, Smith AE, Mohamedali AM, Mian S, Gandhi S, et al. Somatic mutations identify a subgroup of aplastic anemia patients who progress to myelodysplastic syndrome. Blood. 2014;124:2698-704.