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Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations

The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequ...

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Autores principales: Segura-Díaz, Adrián, Stuckey, Ruth, Florido, Yanira, González-Martín, Jesús María, López-Rodríguez, Juan Francisco, Sánchez-Sosa, Santiago, González-Pérez, Elena, Perdomo, María Nieves Sáez, Perera, María del Mar, de la Iglesia, Silvia, Molero-Labarta, Teresa, Gómez-Casares, María Teresa, Bilbao-Sieyro, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226609/
https://www.ncbi.nlm.nih.gov/pubmed/32290079
http://dx.doi.org/10.3390/cancers12040934
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author Segura-Díaz, Adrián
Stuckey, Ruth
Florido, Yanira
González-Martín, Jesús María
López-Rodríguez, Juan Francisco
Sánchez-Sosa, Santiago
González-Pérez, Elena
Perdomo, María Nieves Sáez
Perera, María del Mar
de la Iglesia, Silvia
Molero-Labarta, Teresa
Gómez-Casares, María Teresa
Bilbao-Sieyro, Cristina
author_facet Segura-Díaz, Adrián
Stuckey, Ruth
Florido, Yanira
González-Martín, Jesús María
López-Rodríguez, Juan Francisco
Sánchez-Sosa, Santiago
González-Pérez, Elena
Perdomo, María Nieves Sáez
Perera, María del Mar
de la Iglesia, Silvia
Molero-Labarta, Teresa
Gómez-Casares, María Teresa
Bilbao-Sieyro, Cristina
author_sort Segura-Díaz, Adrián
collection PubMed
description The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequencing (NGS) in an initial cohort of 68 patients with myeloproliferative neoplasms (MPN). As expected, the presence of mutations in DNMT3A, TET2, and ASXL1 (DTA genes) was positively associated with age for the whole cohort (p = 0.025, OR: 1.047, 95% CI: 1.006–1.090). Also, while not related with events in the whole cohort, DTA mutations were strongly associated with the development of vascular events in PV patients (p = 0.028). To confirm the possible association between the presence of DTA mutation and thrombotic events, we performed a case-control study on 55 age-matched patients with PV (including 12 PV patients from the initial cohort, 25 with event vs. 30 no event). In the age-matched case-control PV cohort, the presence of ≥1 DTA mutation significantly increased the risk of a thrombotic event (OR: 6.333, p = 0.0024). Specifically, mutations in TET2 were associated with thrombotic events in the PV case-control cohort (OR: 3.56, 95% CI: 1.15–11.83, p = 0.031). Our results suggest that pathogenic DTA mutations, and particularly TET2 mutations, may be an independent risk factor for thrombosis in patients with PV. However, the predictive value of TET2 and DTA mutations in ET and PMF was inconclusive and should be determined in a larger cohort.
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spelling pubmed-72266092020-05-18 Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations Segura-Díaz, Adrián Stuckey, Ruth Florido, Yanira González-Martín, Jesús María López-Rodríguez, Juan Francisco Sánchez-Sosa, Santiago González-Pérez, Elena Perdomo, María Nieves Sáez Perera, María del Mar de la Iglesia, Silvia Molero-Labarta, Teresa Gómez-Casares, María Teresa Bilbao-Sieyro, Cristina Cancers (Basel) Article The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequencing (NGS) in an initial cohort of 68 patients with myeloproliferative neoplasms (MPN). As expected, the presence of mutations in DNMT3A, TET2, and ASXL1 (DTA genes) was positively associated with age for the whole cohort (p = 0.025, OR: 1.047, 95% CI: 1.006–1.090). Also, while not related with events in the whole cohort, DTA mutations were strongly associated with the development of vascular events in PV patients (p = 0.028). To confirm the possible association between the presence of DTA mutation and thrombotic events, we performed a case-control study on 55 age-matched patients with PV (including 12 PV patients from the initial cohort, 25 with event vs. 30 no event). In the age-matched case-control PV cohort, the presence of ≥1 DTA mutation significantly increased the risk of a thrombotic event (OR: 6.333, p = 0.0024). Specifically, mutations in TET2 were associated with thrombotic events in the PV case-control cohort (OR: 3.56, 95% CI: 1.15–11.83, p = 0.031). Our results suggest that pathogenic DTA mutations, and particularly TET2 mutations, may be an independent risk factor for thrombosis in patients with PV. However, the predictive value of TET2 and DTA mutations in ET and PMF was inconclusive and should be determined in a larger cohort. MDPI 2020-04-10 /pmc/articles/PMC7226609/ /pubmed/32290079 http://dx.doi.org/10.3390/cancers12040934 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Segura-Díaz, Adrián
Stuckey, Ruth
Florido, Yanira
González-Martín, Jesús María
López-Rodríguez, Juan Francisco
Sánchez-Sosa, Santiago
González-Pérez, Elena
Perdomo, María Nieves Sáez
Perera, María del Mar
de la Iglesia, Silvia
Molero-Labarta, Teresa
Gómez-Casares, María Teresa
Bilbao-Sieyro, Cristina
Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations
title Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations
title_full Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations
title_fullStr Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations
title_full_unstemmed Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations
title_short Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations
title_sort thrombotic risk detection in patients with polycythemia vera: the predictive role of dnmt3a/tet2/asxl1 mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226609/
https://www.ncbi.nlm.nih.gov/pubmed/32290079
http://dx.doi.org/10.3390/cancers12040934
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