Similar telomere attrition rates in androgen-treated and untreated patients with dyskeratosis congenita

• Published in: Blood advances Vol. 2; no. 11; pp. 1243 - 1249
• Main Authors: Khincha, Payal P., Bertuch, Alison A., Gadalla, Shahinaz M., Giri, Neelam, Alter, Blanche P., Savage, Sharon A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.06.2018; American Society of Hematology; Elsevier
• Subjects: Adolescent; Adult; Androgens - administration & dosage; Androgens - adverse effects; Child; Child, Preschool; Clinical Trials and Observations; Dyskeratosis Congenita - drug therapy; Dyskeratosis Congenita - metabolism; Dyskeratosis Congenita - pathology; Female; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Middle Aged; Telomere - metabolism; Telomere - pathology; Telomere Homeostasis - drug effects
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2018016964

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and the prototypic telomere biology disorder (TBD). Leukocyte telomere length (TL) less than the first percentile for age, measured by flow cytometry with in situ hybridization (flow FISH), is diagnostic of DC. Androgens are a therapeutic option for DC/TBD-associated bone marrow failure (BMF). One report has shown an apparent increase in TL in patients while on treatment with the attenuated androgen danazol. The aim of this study was to compare TL over time in 10 androgen-treated and 16 untreated patients with DC. All subjects were enrolled in institutional review board–approved longitudinal cohort studies of inherited BMF. TL in 6-panel leukocyte subsets was measured by flow FISH. Generalized estimating equations (GEE) methodology was used to compare TL changes over time between groups. Unadjusted analyses showed annual median total lymphocyte TL attrition of −62 base pairs/year (bp/y) in androgen-treated patients with DC compared with −76 bp/y in untreated DC patients (P = .71). Longitudinal analysis using a GEE model, adjusted for age at sample collection, showed no statistically significant difference in TL change over time between treated and untreated patients (P = .24). The results were similar for each individual leukocyte subset evaluated. In summary, our data show the expected age-associated longitudinal telomere shortening in patients with DC, irrespective of androgen therapy. Caution is warranted when recommending androgen therapy for non-BMF manifestations of DC or TBDs until the biological mechanisms are better understood. •TL for age shortens over time in patients with the TBD DC, irrespective of treatment with androgens.•Prospective long-term research is needed to understand the extra-hematopoietic effects of androgens for management of TBDs. [Display omitted]