Novel DDX41 variants in Thai patients with myeloid neoplasms
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ORIGINAL ARTICLE
Novel DDX41 variants in Thai patients with myeloid neoplasms Chantana Polprasert1,2 · June Takeda3 · Pimjai Niparuck4 · Thanawat Rattanathammethee5 · Arunrat Pirunsarn6 · Amornchai Suksusut1 · Sirorat Kobbuaklee1,2 · Kitsada Wudhikarn1,2 · Panisinee Lawasut1,2 · Sunisa Kongkiatkamon1,2 · Suporn Chuncharunee4 · Kritanan Songserm1 · Prasit Phowthongkum1 · Udomsak Bunworasate1,2 · Yasuhito Nannya3 · Kenichi Yoshida3 · Hideki Makishima3 · Seishi Ogawa3,7,8 · Ponlapat Rojnuckarin1,2 Received: 12 September 2019 / Revised: 27 October 2019 / Accepted: 29 October 2019 © Japanese Society of Hematology 2019
Abstract Germline DDX41 mutations were recently reported to cause MDS/AML and donor-derived leukemia after transplantation. While previously described in Western countries, DDX41 variants have not been reported in a Southeast Asian population. We performed targeted sequencing of blood or bone marrow samples from 109 Thai patients with myeloid malignancies. Among the 109 patients (75 MDS, 8 MPN, 11 MDS/MPN and 15 AML), the most frequent mutations were in ASXL1 (17.4%), TET2 (16.5%) and SRSF2 (12.8%), respectively. DDX41 variants were detectable in six (5.5%) cases. Four patients exhibited three presumable germline DDX41 mutations: p.S21fs (n = 2), p.F235fs (n = 1), and p.R339H (n = 1). While p.S21fs was previously reported in myeloid neoplasm, the latter two variants have not been described. Two of these cases harbored concomitant probable germline/somatic DDX41 mutations (p.S21fs/p.R525H and p.R339H/p.K494T), while the other two patients carried only somatic mutations (p.R525H and p.F438L). The p.K494T and p.F438L variants have not been previously reported. In patients with DDX41 alterations, the diagnoses were MDS with excess blasts (4), secondary AML (1) and low-risk MDS (1). In conclusion, we identified DDX41 variants in Thai patients with myeloid malignancies in which these variants could be used to assess predisposition to MDS in Southeast Asia. Keywords DDX41 alterations · Myelodysplastic syndromes · Acute myeloid leukemia · Southeast asia · Familial MDS/ AML
Introduction Myelodysplastic syndromes (MDS) are typically sporadic disorders affecting the elderly. The disease in younger adults and/or with positive family history is sometimes related to
pre-existing germline mutations. However, familial MDS has been rarely reported. Along with the advances in genetic testing, there is an increasing appreciation of the genetic predisposition syndromes underlying de novo MDS in adult patients. For example, patients with germline RUNX1
* Seishi Ogawa sogawa‑[email protected]
4
Department of Medicine, Faculty of Medicine, Mahidol University Ramathibodi Hospital, Bangkok, Thailand
* Ponlapat Rojnuckarin [email protected]; [email protected]
5
Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
6
Department of Medicine, Buddhasothorn Hospital, Chachengsao, Thailand
7
Institute for the Advanced Study of Human Biology (WPI‑ASHBi), Kyoto Universit
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