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dc.contributor.author | Queirós, Ana C. | - |
dc.contributor.author | González, Marcos | - |
dc.contributor.author | Martín-Subero, José Ignacio | - |
dc.date.accessioned | 2016-06-30T10:06:53Z | - |
dc.date.available | 2016-06-30T10:06:53Z | - |
dc.date.issued | 2015 | - |
dc.identifier | doi: 10.1038/leu.2014.252 | - |
dc.identifier | e-issn: 1476-5551 | - |
dc.identifier | issn: 0887-6924 | - |
dc.identifier.citation | Leukemia 29(3): 598-605 (2015) | - |
dc.identifier.uri | http://hdl.handle.net/10261/134278 | - |
dc.description.abstract | Prospective identification of patients with chronic lymphocytic leukemia (CLL) destined to progress would greatly facilitate their clinical management. Recently, whole-genome DNA methylation analyses identified three clinicobiologic CLL subgroups with an epigenetic signature related to different normal B-cell counterparts. Here, we developed a clinically applicable method to identify these subgroups and to study their clinical relevance. Using a support vector machine approach, we built a prediction model using five epigenetic biomarkers that was able to classify CLL patients accurately into the three subgroups, namely naive B-cell-like, intermediate and memory B-cell-like CLL. DNA methylation was quantified by highly reproducible bisulfite pyrosequencing assays in two independent CLL series. In the initial series (n=211), the three subgroups showed differential levels of IGHV (immunoglobulin heavy-chain locus) mutation (P<0.001) and VH usage (P<0.03), as well as different clinical features and outcome in terms of time to first treatment (TTT) and overall survival (P<0.001). A multivariate Cox model showed that epigenetic classification was the strongest predictor of TTT (P<0.001) along with Binet stage (P<0.001). These findings were corroborated in a validation series (n=97). In this study, we developed a simple and robust method using epigenetic biomarkers to categorize CLLs into three subgroups with different clinicobiologic features and outcome. | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | closedAccess | - |
dc.title | A B-cell epigenetic signature defines three biologic subgroups of chronic lymphocytic leukemia with clinical impact | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1038/leu.2014.252 | - |
dc.date.updated | 2016-06-30T10:06:54Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.relation.csic | Sí | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
item.openairetype | artículo | - |
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