Mutational Profile Enables the Identification of a High-Risk Subgroup in Myelodysplastic Syndromes with Isolated Trisomy 8
Toribio-Castelló, Sofía (CIBERONC. Research Group CB16/12/00233)
Castaño-Díez, Sandra (Hospital Clínic i Provincial de Barcelona)
Villaverde-Ramiro, Ángela (Universidad de Salamanca)
Such, Esperanza (Hospital Universitari i Politècnic La Fe (València))
Arnan, Montserrat (Hospital Duran i Reynals (Hospitalet del Llobregat))
Sole, F (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Díaz-Beyá, Marina (Hospital Clínic i Provincial de Barcelona)
Díez-Campelo, María (CIBERONC. Research Group CB16/12/00233)
del Rey, Mónivs (Hospital Universitario de Salamanca)
González, Teresa (Hospital Universitario de Salamanca)
Hernández-Rivas, Jesús María (CIBERONC. Research Group CB16/12/00233)

Date:	2023
Abstract:	Trisomy 8 (+8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated with clinical heterogeneity and intermediate cytogenetic risk when found in isolation. The presence of gene mutations in this group of patients and the prognostic significance has not been extensively analyzed. Targeted deep sequencing was performed in a cohort of 79 MDS patients showing isolated +8. The most frequently mutated genes were: TET2 (38%), STAG2 (34. 2%), SRSF2 (29. 1%) and RUNX1 (26. 6%). The mutational profile identified a high-risk subgroup with mutations in STAG2, SRSF2 and/or RUNX1, resulting in shorter time to acute myeloid leukemia progression (14 months while not reached in patients without these mutations, p < 0. 0001) and shorter overall survival (23. 7 vs. 46. 3 months, p = 0. 001). Multivariate analyses revealed the presence of mutations in these genes as an independent prognostic factor in MDS showing +8 isolated (HR: 3. 1; p < 0. 01). Moreover, 39. 5% and 15. 4% of patients classified as low/intermediate risk by the IPSS-R and IPSS-M, respectively, were re-stratified as a high-risk subgroup based on the mutational status of STAG2, SRSF2 and RUNX1. Results were validated in an external cohort (n = 2494). In summary, this study validates the prognosis significance of somatic mutations shown in IPSS-M and adds STAG2 as an important mutated gene to consider in this specific subgroup of patients. The mutational profile in isolated +8 MDS patients could, therefore, offer new insights for the correct management of patients with a higher risk of leukemic transformation.
Note:	The research leading to these results has mainly received funding from "Gerencia Regional de Salud de Castilla y León, GRS 2341/A/21 ". In addition, the NEMHESYS project (Grant Agreement 612639-EPP-1-2019-1-ES-EPPKA2-KA), co-funded by the Erasmus+ Programme of the European Union, has trained some of the researchers involved in the work. S.T.C. is a recipient of a predoctoral fellowship from the "Consejería de Educación de la Junta de Castilla y León, EDU/601/2020 " and M.D.R is supported by a fellowship from the Spanish Society of Hematology (FEHH).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Myelodysplastic syndromes ; NGS ; Isolated trisomy 8 ; Prognostic stratification ; AML progression
Published in:	Cancers, Vol. 15 Núm. 15 (august 2023) , p. 3822, ISSN 2072-6694

DOI: 10.3390/cancers15153822
PMID: 37568638

13 p, 1.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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