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Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes.
Sirenko, Maria; Bernard, Elsa; Creignou, Maria; Domenico, Dylan; Farina, Andrea; Arango Ossa, Juan E; Kosmider, Olivier; Hasserjian, Robert; Jädersten, Martin; Germing, Ulrich; Sanz, Guillermo; van de Loosdrecht, Arjan A; Gurnari, Carmelo; Follo, Matilde Yung; Thol, Felicitas; Zamora, Lurdes; Pinheiro, Ronald Feitosa; Pellagatti, Andrea; Elias, Harold K; Haase, Detlef; Sander, Birgitta; Orna, Elisa; Zoldan, Katharina; Eder, Lea Naomi; Sperr, Wolfgang R; Thalhammer, Renate; Ganster, Christina; Adès, Lionel; Tobiasson, Magnus; Palomo, Laura; Della Porta, Matteo Giovanni; Huberman, Kety; Fenaux, Pierre; Belickova, Monika; Savona, Michael R; Klimek, Virginia M; Santos, Fabio P S; Boultwood, Jacqueline; Kotsianidis, Ioannis; Santini, Valeria; Solé, Francesc; Platzbecker, Uwe; Heuser, Michael; Valent, Peter; Finelli, Carlo; Voso, Maria Teresa; Shih, Lee-Yung; Ogawa, Seishi; Fontenay, Michaela; Jansen, Joop H.
Afiliación
  • Sirenko M; Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Bernard E; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Creignou M; Department of Pathology, New York University Grossman School of Medicine, New York, NY.
  • Domenico D; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Farina A; Phase 1 Unit, Center for Clinical Cancer Studies, Karolinska University Hospital, Stockholm, Sweden.
  • Arango Ossa JE; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Kosmider O; Integrated Genomics Operation, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Hasserjian R; Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Jädersten M; Institut Cochin, Université de Paris Cité, Paris, France.
  • Germing U; Hematology Laboratory, Assistance Publique-Hôpitaux de Paris, Centre-Université de Paris Cité, Cochin Hospital, Paris, France.
  • Sanz G; Department of Pathology, Harvard Medical School, Boston, MA.
  • van de Loosdrecht AA; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Gurnari C; Department of Hematology, Oncology and Clinical Immunology, Universitatsklinik Dusseldorf, Dusseldorf, Germany.
  • Follo MY; Department of Hematology, Hospital Universitario y Politécnico La Fe, Health Research Institute La Fe, Valencia, Spain.
  • Thol F; Department of Hematology, Amsterdam University Medical Center, Vrije University Medical Center, Amsterdam, The Netherlands.
  • Zamora L; Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
  • Pinheiro RF; Department of Biomedical and Neuromotor Sciences, Cell Signalling Laboratory, University of Bologna, Bologna, Italy.
  • Pellagatti A; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
  • Elias HK; Hematology Department, Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.
  • Haase D; Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Brazil.
  • Sander B; Radcliffe Department of Medicine, Oxford BRC Haematology Theme, University of Oxford, Oxford, United Kingdom.
  • Orna E; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Zoldan K; Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Eder LN; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Sperr WR; Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
  • Thalhammer R; Hematology Department, Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.
  • Ganster C; Department of Medicine 1, Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany.
  • Adès L; Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany.
  • Tobiasson M; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
  • Palomo L; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
  • Della Porta MG; Department of Laboratory Medicine, Medical University of Vienna, Austria.
  • Huberman K; Clinics of Hematology and Medical Oncology, INDIGHO Laboratories, University Medical Center, Göttingen, Germany.
  • Fenaux P; Department of Hematology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France.
  • Belickova M; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Savona MR; Experimental Hematology Unit, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • Klimek VM; Cancer Center, Humanitas Research Hospital and Humanitas University, Milan, Italy.
  • Santos FPS; Integrated Genomics Operation, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Boultwood J; Department of Hematology, Université de Paris, Saint-Louis Hospital, Paris, France.
  • Kotsianidis I; Department of Genomics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
  • Santini V; Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.
  • Solé F; Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Platzbecker U; Oncology-Hematology Center, Hospital Israelita Albert Einstein, São Paulo, Brazil.
  • Heuser M; Nuffield Division of Clinical Laboratory Sciences, Bloodwise Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
  • Valent P; Department of Hematology, Democritus Thrace University, School of Medicine, Alexandroupolis, Greece.
  • Finelli C; Myelodysplastic Syndromes Unit, Department of Experimental and Clinical Medicine, Hematology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy.
  • Voso MT; Myelodysplastic Syndromes Research Group, Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Spain.
  • Shih LY; Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Leipzig Medical Center, Leipzig, Germany.
  • Ogawa S; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
  • Fontenay M; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
  • Jansen JH; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
Blood ; 144(11): 1221-1229, 2024 09 12.
Article en En | MEDLINE | ID: mdl-38687605
ABSTRACT
ABSTRACT Mutations in UBA1, which are disease-defining for VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, have been reported in patients diagnosed with myelodysplastic syndromes (MDS). Here, we define the prevalence and clinical associations of UBA1 mutations in a representative cohort of patients with MDS. Digital droplet polymerase chain reaction profiling of a selected cohort of 375 male patients lacking MDS disease-defining mutations or established World Health Organization (WHO) disease classification identified 28 patients (7%) with UBA1 p.M41T/V/L mutations. Using targeted sequencing of UBA1 in a representative MDS cohort (n = 2027), we identified an additional 27 variants in 26 patients (1%), which we classified as likely/pathogenic (n = 12) and of unknown significance (n = 15). Among the total 40 patients with likely/pathogenic variants (2%), all were male and 63% were classified by WHO 2016 criteria as MDS with multilineage dysplasia or MDS with single-lineage dysplasia. Patients had a median of 1 additional myeloid gene mutation, often in TET2 (n = 12), DNMT3A (n = 10), ASXL1 (n = 3), or SF3B1 (n = 3). Retrospective clinical review, where possible, showed that 82% (28/34) UBA1-mutant cases had VEXAS syndrome-associated diagnoses or inflammatory clinical presentation. The prevalence of UBA1 mutations in patients with MDS argues for systematic screening for UBA1 in the management of MDS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Mielodisplásicos / Enzimas Activadoras de Ubiquitina / Mutación Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Mielodisplásicos / Enzimas Activadoras de Ubiquitina / Mutación Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos