A Yoshimi1, T Toya1, Y Nannya1, K Takaoka1, K Kirito2, E Ito3, H Nakajima4, Y Hayashi5, T Takahashi6, A Moriya-Saito7, K Suzuki8, H Harada9, N Komatsu10, K Usuki11, M Ichikawa1, M Kurokawa12. 1. Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo. 2. Department of Hematology and Oncology, University of Yamanashi, Yamanashi. 3. Department of Pediatrics, Graduate School of Medicine, Hirosaki University, Aomori. 4. Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo. 5. Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma. 6. The Department of Hematology, Mitsui Memorial Hospital, Tokyo. 7. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi. 8. Department of Hematology, Japanese Red Cross Medical Center, Tokyo. 9. Department of Hematology, Graduate School of Medicine, Juntendo University, Tokyo Department of Hematology and Oncology, Hiroshima University, Hiroshima. 10. Department of Hematology, Graduate School of Medicine, Juntendo University, Tokyo. 11. Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan. 12. Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo kurokawa-tky@umin.ac.jp.
Abstract
BACKGROUND: Inherited thrombocytopenia (IT) contains several forms of familial thrombocytopenia and some of them have propensity to hematological malignancies. The etiological and genetic features of this heterogeneous syndrome have not yet been elucidated. PATIENTS AND METHODS: We conducted a nationwide survey to collect clinical information and samples from patients with familial thrombocytopenia and/or hematological malignancies in order to obtain a comprehensive understanding of IT. RESULTS: Among the 43 pedigrees with clinical samples, RUNX1 mutations were identified in 8 pedigrees (18.6%). While MYH9 and ANKRD26 mutations were identified in 2 and 1 pedigrees, respectively, no gene mutations were detected in the remaining 32 pedigrees from a panel of previously reported pathogenetic mutations. Clinical data were comparable between FPD/AML and non-FPD/AML probands. CONCLUSIONS: Our study clarified that it is unexpectedly difficult to diagnose FPD/AML based on clinical information alone, and thus, genetic testing is strongly recommended. Our survey also identified some pedigrees with a strong family history of myelodysplastic syndromes of unknown origin. Additionally, there were 14 pedigrees in which three or more members were affected by immune thrombocytopenia (ITP), and a computer-aided simulation suggested that such a distribution almost never happens by coincidence, which implicates a genetic predisposition to ITP.
BACKGROUND: Inherited thrombocytopenia (IT) contains several forms of familial thrombocytopenia and some of them have propensity to hematological malignancies. The etiological and genetic features of this heterogeneous syndrome have not yet been elucidated. PATIENTS AND METHODS: We conducted a nationwide survey to collect clinical information and samples from patients with familial thrombocytopenia and/or hematological malignancies in order to obtain a comprehensive understanding of IT. RESULTS: Among the 43 pedigrees with clinical samples, RUNX1 mutations were identified in 8 pedigrees (18.6%). While MYH9 and ANKRD26 mutations were identified in 2 and 1 pedigrees, respectively, no gene mutations were detected in the remaining 32 pedigrees from a panel of previously reported pathogenetic mutations. Clinical data were comparable between FPD/AML and non-FPD/AML probands. CONCLUSIONS: Our study clarified that it is unexpectedly difficult to diagnose FPD/AML based on clinical information alone, and thus, genetic testing is strongly recommended. Our survey also identified some pedigrees with a strong family history of myelodysplastic syndromes of unknown origin. Additionally, there were 14 pedigrees in which three or more members were affected by immune thrombocytopenia (ITP), and a computer-aided simulation suggested that such a distribution almost never happens by coincidence, which implicates a genetic predisposition to ITP.
Authors: Rashmi Kanagal-Shamanna; Sanam Loghavi; Courtney D DiNardo; L Jeffrey Medeiros; Guillermo Garcia-Manero; Elias Jabbour; Mark J Routbort; Rajyalakshmi Luthra; Carlos E Bueso-Ramos; Joseph D Khoury Journal: Haematologica Date: 2017-06-28 Impact factor: 9.941
Authors: Hrushikesh Vyas; Ahmad Alcheikh; Gillian Lowe; William S Stevenson; Neil V Morgan; David J Rabbolini Journal: Platelets Date: 2022-05-19 Impact factor: 4.236
Authors: Anna L Brown; Peer Arts; Catherine L Carmichael; Milena Babic; Julia Dobbins; Chan-Eng Chong; Andreas W Schreiber; Jinghua Feng; Kerry Phillips; Paul P S Wang; Thuong Ha; Claire C Homan; Sarah L King-Smith; Lesley Rawlings; Cassandra Vakulin; Andrew Dubowsky; Jessica Burdett; Sarah Moore; Grace McKavanagh; Denae Henry; Amanda Wells; Belinda Mercorella; Mario Nicola; Jeffrey Suttle; Ella Wilkins; Xiao-Chun Li; Joelle Michaud; Peter Brautigan; Ping Cannon; Meryl Altree; Louise Jaensch; Miriam Fine; Carolyn Butcher; Richard J D'Andrea; Ian D Lewis; Devendra K Hiwase; Elli Papaemmanuil; Marshall S Horwitz; Georges Natsoulis; Hugh Y Rienhoff; Nigel Patton; Sally Mapp; Rachel Susman; Susan Morgan; Julian Cooney; Mark Currie; Uday Popat; Tilmann Bochtler; Shai Izraeli; Kenneth Bradstock; Lucy A Godley; Alwin Krämer; Stefan Fröhling; Andrew H Wei; Cecily Forsyth; Helen Mar Fan; Nicola K Poplawski; Christopher N Hahn; Hamish S Scott Journal: Blood Adv Date: 2020-03-24