Clinical, biological, and prognostic implications of SF3B1 co-occurrence mutations in very low/low- and intermediate-risk MDS patients

Janusz, Kamila; Izquierdo, M.; Cadenas, Félix López; Ramos, Fernando; Hernández-Sánchez, Jesús M; Lumbreras, Eva; Robledo, Cristina; Real, Javier Sánchez del; Caballero, Juan Carlos; Collado, Rosa; Bernal, Teresa; Pedro, Carme; Insunza, Andrés; Paz, Raquel de; Xicoy, Blanca; García, J Sánchez; Mínguez, Sandra Santos; García, Cristina Miguel; Muñoz, Ana; Barba, Mercedes Sánchez; Rivas, Jesús Marı́a Hernández; Abáigar, María; Díez-Campelo, Maria

doi:10.1007/s00277-020-04360-4

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…Remarkably, the proportion of patients with isolated + 8 MDS and mutations in STAG2 was near three times more that in control MDS as previously reported (14). As expected, the incidence of mutations in SF3B1 was lower in the isolated + 8 cohort compared to control MDS due to these mutations have been extensively associated to MDS with ring sideroblasts (22)(23)(24) or normal karyotypes (25), which is concordant to the low incidence of these alterations in our cohort. By contrast, our results did not show TP53 as frequently mutated in MDS with isolated + 8, which was consistent with the high association of mutations in this gene to both complex karyotype and 5q deletion previously described in MDS(26-28).…”

Section: Discussionsupporting

confidence: 91%

Mutational Profile Enables the Identification of a High Risk Subgroup in Myelodysplastic Syndromes With Isolated Trisomy 8

Toribio-Castelló

Castaño-Díez

Ramiro

et al. 2023

Preprint

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Trisomy 8 (+ 8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated to clinical heterogeneity and intermediate cytogenetic risk when found isolated. 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 + 8isolated (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 high risk subgroup based on the mutational status of STAG2, SRSF2 and RUNX1. Results were validated in an external cohort (n = 2 494). In summary, the mutational profile in isolated + 8 MDS patients could offer new insights for the correct management of these patients.

show abstract

Section: Discussionsupporting

confidence: 91%

Mutational Profile Enables the Identification of a High Risk Subgroup in Myelodysplastic Syndromes With Isolated Trisomy 8

Toribio-Castelló

Castaño-Díez

Ramiro

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Remarkably, the proportion of patients with isolated +8 MDS and mutations in STAG2 was near three times more that in control MDS as previously reported 12 . As expected, the incidence of mutations in SF3B1 was lower in the isolated +8 cohort compared to control MDS due to these mutations have been extensively associated to MDS with ring sideroblasts 20–22 or normal karyotypes 23 , which is concordant to the low incidence of these alterations in our cohort. By contrast, our results did not show TP53 as frequently mutated in MDS with isolated +8, which was consistent with the high association of mutations in this gene to both complex karyotype and 5q deletion previously described in MDS 24–26 .…”

Section: Discussionsupporting

confidence: 88%

Mutational Profile Enables the Identification of a High Risk Subgroup in Myelodysplastic Syndromes With Isolated Trisomy 8

Castelló

Castano

Villaverde

et al. 2023

Preprint

View full text Add to dashboard Cite

Trisomy 8 (+8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated to clinical heterogeneity and intermediate cytogenetic risk when found isolated. 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 more frequent 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 +8i (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 high risk subgroup based on the mutational status of STAG2, SRSF2 and RUNX1. Results were validated in an external cohort. In summary, the mutational profile in isolated +8 MDS patients could offer new insights for the correct management of these patients.

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“…The frequency of co-mutation of ASXL1 and SF3B1 is reported to be low (approximately 8%) (36) and even mutually exclusive by some authors [reviewed in (20)]. There are also very few and inconsistent reports about the clinical prognosis of ASXL1/SF3B1 co-mutations (20,64,65). All the previous studies also included patients with mutations of genes other than ASXL1 and SF3B1, which could significantly confound the analysis and skew the results.…”

Section: Discussionmentioning

confidence: 99%

Co-mutation ofASXL1andSF3B1Predicts Poorer Overall Survival Than IsolatedASXL1orSF3B1Mutations

Song¹,

Moscinski²,

Yang³

et al. 2023

In Vivo

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Clinical, biological, and prognostic implications of SF3B1 co-occurrence mutations in very low/low- and intermediate-risk MDS patients

Cited by 11 publications

References 35 publications

Mutational Profile Enables the Identification of a High Risk Subgroup in Myelodysplastic Syndromes With Isolated Trisomy 8

Mutational Profile Enables the Identification of a High Risk Subgroup in Myelodysplastic Syndromes With Isolated Trisomy 8

Mutational Profile Enables the Identification of a High Risk Subgroup in Myelodysplastic Syndromes With Isolated Trisomy 8

Co-mutation ofASXL1andSF3B1Predicts Poorer Overall Survival Than IsolatedASXL1orSF3B1Mutations

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