Kirschner, Martin and Maurer, Angela and Wlodarski, Marcin W. and Ferreira, Monica S. Ventura and Bouillon, Anne-Sophie and Halfmeyer, Insa and Blau, Wolfgang and Kreuter, Michael and Rosewich, Martin and Corbacioglu, Selim and Beck, Joachim and Schwarz, Michaela and Bittenbring, Joerg and Radsak, Markus P. and Wilk, Christian Matthias and Koschmieder, Steffen and Begemann, Matthias and Kurth, Ingo and Schemionek, Mirle and Bruemmendorf, Tim H. and Beier, Fabian (2018) Recurrent somatic mutations are rare in patients with cryptic dyskeratosis congenita. LEUKEMIA, 32 (8). pp. 1762-1767. ISSN 0887-6924, 1476-5551
Full text not available from this repository. (Request a copy)Abstract
Dyskeratosis congenita (DKC) is a paradigmatic telomere disorder characterized by substantial and premature telomere shortening, bone marrow failure, and a dramatically increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). DKC can occur as a late-onset, so-called cryptic form, with first manifestation in adults. Somatic MDS-related mutations are found in up to 35% of patients with acquired aplastic anemia (AA), especially in patients with short telomeres. The aim of our study was to investigate whether cryptic DKC is associated with an increased incidence of MDS-related somatic mutations, thereby linking the accelerated telomere shortening with the increased risk of MDS/AML. Samples from 15 adult patients (median age: 42 years, range: 23-60 years) with molecularly confirmed cryptic DKC were screened using next-generation gene panel sequencing to detect MDS-related somatic variants. Only one of the 15 patients (7%) demonstrated a clinically relevant MDS-related somatic variant. This incidence was dramatically lower than formerly described in acquired AA. Based on our data, we conclude that clonal evolution of subclones carrying MDS-related mutations is not the predominant mechanism for MDS/AML initiation in adult cryptic DKC patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLONAL HEMATOPOIESIS; TELOMERE LENGTH; APLASTIC-ANEMIA; MYELODYSPLASTIC SYNDROMES; MYELOID-LEUKEMIA; DISEASE; CANCER; AGE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2020 13:10 |
| Last Modified: | 06 Apr 2020 05:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14156 |
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