دورية أكاديمية
Diagnostic capabilities, clinical features, and longitudinal UBA1 clonal dynamics of a nationwide VEXAS cohort.
| العنوان: | Diagnostic capabilities, clinical features, and longitudinal UBA1 clonal dynamics of a nationwide VEXAS cohort. |
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| المؤلفون: | Gurnari C; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.; Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio, USA., Pascale MR; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy., Vitale A; Rheumatology Unit, Department of Medical Sciences, Surgery and Neurosciences, University of Siena and Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy., Diral E; Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Tomelleri A; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy., Galossi E; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy., Falconi G; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy., Bruno A; Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Crisafulli F; ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy., Frassi M; ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy., Cattaneo C; ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy., Bertoli D; ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy., Bernardi M; Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Condorelli A; Azienda SocioSanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy., Morsia E; Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy., Poloni A; Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy., Crisà E; Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Caravelli D; Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Triggianese P; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy., Brussino L; Department of Medical Sciences Allergy and Clinical Immunology Unit, University of Torino & Mauriziano Hospital, Torino, Italy., Battipaglia G; Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy., Bindoli S; Rheumatology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy., Sfriso P; Rheumatology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy., Caroni F; Hematology, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy., Dragani M; IRCCS San Martino Hospital, Genova, Italy., Mallegni F; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy., Pilo F; Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy., Firinu D; Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy., Curti A; Istituto di Ematologia 'Seràgnoli', IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Papayannidis C; Istituto di Ematologia 'Seràgnoli', IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Olivieri A; Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy., Kordasti S; Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.; Haematology, Guy's Hospital & Comprehensive Cancer Centre, King's College, London, UK., Albano F; Department of Precision and Regenerative Medicine and Ionian Area, 'Aldo Moro' University, Bari, Italy., Pane F; Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy., Musto P; Department of Precision and Regenerative Medicine and Ionian Area, 'Aldo Moro' University, Bari, Italy., Bocchia M; Hematology, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy., Lugli E; Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy., Breccia M; Department of Translational and Precision Medicine, Policlinico Umberto I, Sapienza University, Rome, Italy., Frigeni M; Azienda SocioSanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy., Dagna L; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy., Greco R; Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Franceschini F; ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy., Campochiaro C; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy., Cantarini L; Rheumatology Unit, Department of Medical Sciences, Surgery and Neurosciences, University of Siena and Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy., Voso MT; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy. |
| المصدر: | American journal of hematology [Am J Hematol] 2024 Feb; Vol. 99 (2), pp. 254-262. Date of Electronic Publication: 2023 Dec 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 7610369 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-8652 (Electronic) Linking ISSN: 03618609 NLM ISO Abbreviation: Am J Hematol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Wiley-Blackwell Original Publication: New York, Liss. |
| مواضيع طبية MeSH: | Hematopoietic Stem Cell Transplantation* , Myelodysplastic Syndromes*/diagnosis , Myelodysplastic Syndromes*/genetics , Myelodysplastic Syndromes*/therapy , Leukemia* , Arthritis, Rheumatoid* , Skin Diseases, Genetic*, Humans ; Male ; Aged ; Mutation |
| مستخلص: | VEXAS is a prototypic hemato-inflammatory disease combining rheumatologic and hematologic disorders in a molecularly defined nosological entity. In this nationwide study, we aimed at screenshotting the current diagnostic capabilities and clinical-genomic features of VEXAS, and tracked UBA1 longitudinal clonal dynamics upon different therapeutics, including allogeneic hematopoietic cell transplant. We leveraged a collaboration between the Italian Society of Experimental Hematology and of Rheumatology and disseminated a national survey to collect clinical and molecular patient information. Overall, 13/29 centers performed UBA1 genomic testing locally, including Sanger sequencing (46%), next-generation sequencing (23%), droplet digital polymerase chain reaction (8%), or combination (23%). A total of 41 male patients were identified, majority (51%) with threonine substitutions at Met41 hotspot, followed by valine and leucine (27% and 8%). Median age at VEXAS diagnosis was 67 years. All patients displayed anemia (median hemoglobin 9.1 g/dL), with macrocytosis. Bone marrow vacuoles were observed in most cases (89%). The most common rheumatologic association was polychondritis (49%). A concomitant myelodysplastic neoplasm/syndrome (MDS) was diagnosed in 71% of patients (n = 28), chiefly exhibiting lower Revised International Prognostic Scoring System risk profiles. Karyotype was normal in all patients, except three MDS cases showing -Y, t(12;16)(q13;q24), and +8. The most frequently mutated gene was DNMT3A (n = 10), followed by TET2 (n = 3). At last follow-up, five patients died and two patients progressed to acute leukemia. Longitudinal UBA1 clonal dynamics demonstrated mutational clearance following transplant. We collected a nationwide interdisciplinary VEXAS patient cohort, characterized by heterogeneous rheumatologic manifestations and treatments used. MDS was diagnosed in 71% of cases. Patients exhibited various longitudinal UBA1 clonal dynamics. (© 2023 Wiley Periodicals LLC.) |
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| معلومات مُعتمدة: | 21267 AIRC 5×1000; Myeloid Neoplasms Research Venture AIRC; 2017WXR7ZT MUR-PNRR M4C2I1.3 PE6 project PE00000019 Heal Italia; Finalizzata 2018 NET-2018-12365935 Ministero della Salute; Edward P. Evans Foundation |
| SCR Disease Name: | VEXAS syndrome |
| تواريخ الأحداث: | Date Created: 20231218 Date Completed: 20240122 Latest Revision: 20240122 |
| رمز التحديث: | 20240122 |
| DOI: | 10.1002/ajh.27169 |
| PMID: | 38108611 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-8652 |
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| DOI: | 10.1002/ajh.27169 |