Adrián Segura-Díaz, Ruth Stuckey, Yanira Florido, Marta Sobas, Alberto Álvarez-Larrán, Francisca Ferrer-Marín, Manuel Pérez-Encinas, Gonzalo Carreño-Tarragona, María L Fox, Barbara Tazón Vega, Beatriz Cuevas, Juan F López Rodríguez, Nuria Sánchez-Farías, Jesús M González-Martín, María T Gómez-Casares, Cristina Bilbao-Sieyro
{"title":"DNMT3A/TET2/ASXL1突变是多发性红细胞症患者中与年龄无关的血栓风险因素:一项观察性研究。","authors":"Adrián Segura-Díaz, Ruth Stuckey, Yanira Florido, Marta Sobas, Alberto Álvarez-Larrán, Francisca Ferrer-Marín, Manuel Pérez-Encinas, Gonzalo Carreño-Tarragona, María L Fox, Barbara Tazón Vega, Beatriz Cuevas, Juan F López Rodríguez, Nuria Sánchez-Farías, Jesús M González-Martín, María T Gómez-Casares, Cristina Bilbao-Sieyro","doi":"10.1055/a-2239-9265","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong> Polycythemia vera (PV) patients are classified as high or low thrombotic risk based on age and prior history of thrombosis. Despite adherence to treatment recommendations, vascular events remain frequent, leading us to question whether thrombotic risk stratification could be improved. We previously reported an association between thrombotic events and mutations in DTA genes (<i>DNMT3A, TET2,</i> and <i>ASXL1</i>). The objective of this study was to confirm this observation in a larger series of PV patients.</p><p><strong>Methods: </strong> PV patients with a minimum follow-up of 3 years were recruited from 8 European centers. Medical history was searched for thrombotic event recorded at any time and next-generation sequencing carried out with a myeloid panel. Multivariable logistic regression evaluated the impact of variables on thrombotic risk. Kaplan-Meier thrombosis-free survival curves were compared by the log rank test. Associations in the total cohort were confirmed in a case-control study to exclude selection bias.</p><p><strong>Results: </strong> Of the 136 patients recruited, 74 (56.1%) had a thrombotic event, with an incidence density of 2.83/100 person-years. In multivariable analysis, DTA mutation was a risk factor for thrombotic event, being predictive for shorter thrombosis-free survival in the whole cohort (<i>p</i> = 0.007), as well as in low-risk patients (<i>p</i> = 0.039) and older patients (<i>p</i> = 0.009), but not for patients with a prediagnostic event. A gender- and age-matched case-control study confirmed the increased risk of thrombotic event for PV patients with a DTA mutation.</p><p><strong>Conclusion: </strong> Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199052/pdf/","citationCount":"0","resultStr":"{\"title\":\"DNMT3A/TET2/ASXL1 Mutations are an Age-independent Thrombotic Risk Factor in Polycythemia Vera Patients: An Observational Study.\",\"authors\":\"Adrián Segura-Díaz, Ruth Stuckey, Yanira Florido, Marta Sobas, Alberto Álvarez-Larrán, Francisca Ferrer-Marín, Manuel Pérez-Encinas, Gonzalo Carreño-Tarragona, María L Fox, Barbara Tazón Vega, Beatriz Cuevas, Juan F López Rodríguez, Nuria Sánchez-Farías, Jesús M González-Martín, María T Gómez-Casares, Cristina Bilbao-Sieyro\",\"doi\":\"10.1055/a-2239-9265\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong> Polycythemia vera (PV) patients are classified as high or low thrombotic risk based on age and prior history of thrombosis. Despite adherence to treatment recommendations, vascular events remain frequent, leading us to question whether thrombotic risk stratification could be improved. We previously reported an association between thrombotic events and mutations in DTA genes (<i>DNMT3A, TET2,</i> and <i>ASXL1</i>). The objective of this study was to confirm this observation in a larger series of PV patients.</p><p><strong>Methods: </strong> PV patients with a minimum follow-up of 3 years were recruited from 8 European centers. Medical history was searched for thrombotic event recorded at any time and next-generation sequencing carried out with a myeloid panel. Multivariable logistic regression evaluated the impact of variables on thrombotic risk. Kaplan-Meier thrombosis-free survival curves were compared by the log rank test. Associations in the total cohort were confirmed in a case-control study to exclude selection bias.</p><p><strong>Results: </strong> Of the 136 patients recruited, 74 (56.1%) had a thrombotic event, with an incidence density of 2.83/100 person-years. In multivariable analysis, DTA mutation was a risk factor for thrombotic event, being predictive for shorter thrombosis-free survival in the whole cohort (<i>p</i> = 0.007), as well as in low-risk patients (<i>p</i> = 0.039) and older patients (<i>p</i> = 0.009), but not for patients with a prediagnostic event. A gender- and age-matched case-control study confirmed the increased risk of thrombotic event for PV patients with a DTA mutation.</p><p><strong>Conclusion: </strong> Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.</p>\",\"PeriodicalId\":23036,\"journal\":{\"name\":\"Thrombosis and haemostasis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199052/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Thrombosis and haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1055/a-2239-9265\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Thrombosis and haemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1055/a-2239-9265","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/8 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
DNMT3A/TET2/ASXL1 Mutations are an Age-independent Thrombotic Risk Factor in Polycythemia Vera Patients: An Observational Study.
Background: Polycythemia vera (PV) patients are classified as high or low thrombotic risk based on age and prior history of thrombosis. Despite adherence to treatment recommendations, vascular events remain frequent, leading us to question whether thrombotic risk stratification could be improved. We previously reported an association between thrombotic events and mutations in DTA genes (DNMT3A, TET2, and ASXL1). The objective of this study was to confirm this observation in a larger series of PV patients.
Methods: PV patients with a minimum follow-up of 3 years were recruited from 8 European centers. Medical history was searched for thrombotic event recorded at any time and next-generation sequencing carried out with a myeloid panel. Multivariable logistic regression evaluated the impact of variables on thrombotic risk. Kaplan-Meier thrombosis-free survival curves were compared by the log rank test. Associations in the total cohort were confirmed in a case-control study to exclude selection bias.
Results: Of the 136 patients recruited, 74 (56.1%) had a thrombotic event, with an incidence density of 2.83/100 person-years. In multivariable analysis, DTA mutation was a risk factor for thrombotic event, being predictive for shorter thrombosis-free survival in the whole cohort (p = 0.007), as well as in low-risk patients (p = 0.039) and older patients (p = 0.009), but not for patients with a prediagnostic event. A gender- and age-matched case-control study confirmed the increased risk of thrombotic event for PV patients with a DTA mutation.
Conclusion: Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.
期刊介绍:
Thrombosis and Haemostasis publishes reports on basic, translational and clinical research dedicated to novel results and highest quality in any area of thrombosis and haemostasis, vascular biology and medicine, inflammation and infection, platelet and leukocyte biology, from genetic, molecular & cellular studies, diagnostic, therapeutic & preventative studies to high-level translational and clinical research. The journal provides position and guideline papers, state-of-the-art papers, expert analysis and commentaries, and dedicated theme issues covering recent developments and key topics in the field.