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http://hdl.handle.net/10261/135790
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dc.contributor.author | Paiva, Bruno | - |
dc.contributor.author | Corchete, Luis A. | - |
dc.contributor.author | Vidriales, Maria Belén | - |
dc.contributor.author | García-Sanz, Ramón | - |
dc.contributor.author | Pérez, José J. | - |
dc.contributor.author | Aires-Mejia, I. | - |
dc.contributor.author | Sánchez, Maria Luz | - |
dc.contributor.author | Bárcena, Paloma | - |
dc.contributor.author | Jiménez, Cristina | - |
dc.contributor.author | Sarasquete, María Eugenia | - |
dc.contributor.author | Mateos, Maria Victoria | - |
dc.contributor.author | Ocio, Enrique M. | - |
dc.contributor.author | Puig, Noemi | - |
dc.contributor.author | García de Coca, Alfonso | - |
dc.contributor.author | Orfao, Alberto | - |
dc.contributor.author | Gutiérrez, Norma Carmen | - |
dc.contributor.author | San Miguel, Jesús F. | - |
dc.date.accessioned | 2016-08-23T11:27:55Z | - |
dc.date.available | 2016-08-23T11:27:55Z | - |
dc.date.issued | 2015 | - |
dc.identifier | doi: 10.1182/blood-2014-09-602565 | - |
dc.identifier | e-issn: 1528-0020 | - |
dc.identifier | issn: 0006-4971 | - |
dc.identifier.citation | Blood 125(15): 2370-2380 (2015) | - |
dc.identifier.uri | http://hdl.handle.net/10261/135790 | - |
dc.description.abstract | Although information about the molecular pathogenesis of Waldenström macroglobulinemia (WM) has significantly advanced, the precise cell of origin and the mechanisms behind WM transformation from immunoglobulin-M (IgM) monoclonal gammopathy of undetermined significance (MGUS) remain undetermined. Here, we undertook an integrative phenotypic, molecular, and genomic approach to study clonal B cells from newly diagnosed patients with IgM MGUS (n = 22), smoldering (n = 16), and symptomatic WM (n = 11). Through principal component analysis of multidimensional flow cytometry data, we demonstrated highly overlapping phenotypic profiles for clonal B cells from IgM MGUS, smoldering, and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between fluorescence-activated cell sorter-sorted clonal B cells from the 3 disease groups. Interestingly, the transcriptome of the Waldenström B-cell clone was highly different than that of normal CD25<sup>-</sup>CD22<sup>+</sup> B cells, whereas significantly less genes were differentially expressed and specific WM pathways normalized once the transcriptome of the Waldenström B-cell clone was compared with its normal phenotypic (CD25<sup>+</sup>CD22<sup>+low</sup>) B-cell counterpart. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs symptomatic WM (18% vs 20% and 73%, respectively; P = .008), suggesting a multistep transformation of clonal B cells that, albeit benign (ie, IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström clone. | - |
dc.description.sponsorship | This study was supported by Cooperative Research Thematic Network grants RD12/0036/0058 and RD12/0036/0048 of the Red de Cancer (Cancer Network of Excellence), Consejería de Sanidad, Junta de Castilla y Leon, Valladolid, Spain (557/A/10). | - |
dc.publisher | American Society of Hematology | - |
dc.rights | closedAccess | - |
dc.title | The cellular origin and malignant transformation of Waldenström macroglobulinemia | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1182/blood-2014-09-602565 | - |
dc.date.updated | 2016-08-23T11:27:55Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.contributor.funder | Red Temática de Investigación Cooperativa en Cáncer (España) | - |
dc.contributor.funder | Junta de Castilla y León | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100014180 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
item.openairetype | artículo | - |
item.fulltext | No Fulltext | - |
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