Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes Journal Article

   


Authors: Sirenko, M.; Bernard, E.; Creignou, M.; Domenico, D.; Farina, A.; Arango Ossa, J. E.; Kosmider, O.; Hasserjian, R.; Jädersten, M.; Germing, U.; Sanz, G.; van de Loosdrecht, A. A.; Gurnari, C.; Follo, M. Y.; Thol, F.; Zamora, L.; Pinheiro, R. F.; Pellagatti, A.; Elias, H. K.; Haase, D.; Sander, B.; Orna, E.; Zoldan, K.; Eder, L. N.; Sperr, W. R.; Thalhammer, R.; Ganster, C.; Adès, L.; Tobiasson, M.; Palomo, L.; Della Porta, M. G.; Huberman, K.; Fenaux, P.; Belickova, M.; Savona, M. R.; Klimek, V. M.; Santos, F. P. S.; Boultwood, J.; Kotsianidis, I.; Santini, V.; Solé, F.; Platzbecker, U.; Heuser, M.; Valent, P.; Finelli, C.; Voso, M. T.; Shih, L. Y.; Ogawa, S.; Fontenay, M.; Jansen, J. H.; Cervera, J.; Ebert, B. L.; Bejar, R.; Greenberg, P. L.; Gattermann, N.; Malcovati, L.; Cazzola, M.; Beck, D. B.; Hellström-Lindberg, E.; Papaemmanuil, E.
Article Title: Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes
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. © 2024 American Society of Hematology
Keywords: adult; clinical article; aged; aged, 80 and over; middle aged; young adult; gene mutation; genetics; mutation; clinical feature; disease classification; gene; ubiquitin protein ligase; prevalence; cohort analysis; retrospective study; myelodysplastic syndrome; diagnosis; ubiquitin-activating enzymes; myelodysplastic syndromes; tet2 gene; dna methyltransferase 3a; refractory cytopenia with multilineage dysplasia; very elderly; humans; human; male; female; article; droplet digital polymerase chain reaction; refractory cytopenia with unilineage dysplasia; uba1 protein, human; uba1 gene
Journal Title: Blood
Volume: 144
Issue: 11
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2024-09-12
Start Page: 1221
End Page: 1229
Language: English
DOI: 10.1182/blood.2023023723
PUBMED: 38687605
PROVIDER: scopus
PMCID: PMC12060156
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85201320044&doi=10.1182%2fblood.2023023723&partnerID=40&md5=c637f77a0d587bf6ef4e55dd79613a45
Notes: Article -- Source: Scopus
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MSK Authors
  1. Virginia Klimek
    147 Klimek
  2. Andrea Farina
    15 Farina
  3. Kety H Huberman
    34 Huberman
  4. Elli Papaemmanuil
    206 Papaemmanuil
  5. Harold Kunal Elias
    15 Elias
  6. Elsa Bernard
    49 Bernard
  7. Maria Sirenko
    13 Sirenko
  8. Juan Esteban Arango Ossa
    48 Arango Ossa
  9. Dylan Michael Domenico
    15 Domenico
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