000070603 001__ 70603
000070603 005__ 20200221144339.0
000070603 0247_ $$2doi$$a10.1182/blood-2015-10-673095
000070603 0248_ $$2sideral$$a106067
000070603 037__ $$aART-2016-106067
000070603 041__ $$aeng
000070603 100__ $$aPaiva, B.
000070603 245__ $$aPhenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis
000070603 260__ $$c2016
000070603 5060_ $$aAccess copy available to the general public$$fUnrestricted
000070603 5203_ $$aImmunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are 2 distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite the fact that knowledge about MM PC biology has significantly increased in the last decade, the same does not apply for AL. Here, we used an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 24 newly diagnosed patients with AL. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and both monoclonal gammopathy of undetermined significance and MM PCs. However, in contrast to MM, highly purified fluorescence-activated cell-sorted clonal PCs from AL (n = 9) showed almost normal transcriptome, with only 38 deregulated genes vs normal PCs; these included a few tumor-suppressor (CDH1, RCAN) and proapoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n=11) were genomically unstable, with a median of 9 copy number alterations (CNAs) per case, many of such CNAs being similar to those found in MM. Whole-exome sequencing (WES) performed in 5 AL patients revealed a median of 15 nonrecurrent mutations per case. Altogether, our results show that in the absence of a unifying mutation by WES, clonal PCs in AL display phenotypic and CNA profiles similar to MM, but their transcriptome is remarkably similar to that of normal PCs.
000070603 536__ $$9info:eu-repo/grantAgreement/ES/FIS/PI13-02196
000070603 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000070603 590__ $$a13.164$$b2016
000070603 591__ $$aHEMATOLOGY$$b2 / 70 = 0.029$$c2016$$dQ1$$eT1
000070603 592__ $$a5.918$$b2016
000070603 593__ $$aBiochemistry$$c2016$$dQ1
000070603 593__ $$aImmunology$$c2016$$dQ1
000070603 593__ $$aHematology$$c2016$$dQ1
000070603 593__ $$aCell Biology$$c2016$$dQ1
000070603 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000070603 700__ $$aMartinez-Lopez, J.
000070603 700__ $$aCorchete, L.A.
000070603 700__ $$aSanchez-Vega, B.
000070603 700__ $$aRapado, I.
000070603 700__ $$aPuig, N.
000070603 700__ $$aBarrio, S.
000070603 700__ $$aSanchez, M.L.
000070603 700__ $$aAlignani, D.
000070603 700__ $$aLasa, M.
000070603 700__ $$ade Coca, A.G.
000070603 700__ $$aPardal, E.
000070603 700__ $$aOriol, A.
000070603 700__ $$aGarcia, M.E.G.
000070603 700__ $$aEscalante, F.
000070603 700__ $$aGonzalez-Lopez, T.J.
000070603 700__ $$0(orcid)0000-0001-8515-3599$$aPalomera, L.$$uUniversidad de Zaragoza
000070603 700__ $$aAlonso, J.
000070603 700__ $$aProsper, F.
000070603 700__ $$aOrfao, A.
000070603 700__ $$aVidriales, M.B.
000070603 700__ $$aMateos, M.V.
000070603 700__ $$aLahuerta, J.J.
000070603 700__ $$aGutierrez, N.C.
000070603 700__ $$aSan Miguel, J.F.
000070603 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000070603 773__ $$g127, 24 (2016), 3035-3039$$pBlood$$tBLOOD$$x0006-4971
000070603 8564_ $$s651005$$uhttps://zaguan.unizar.es/record/70603/files/texto_completo.pdf$$yVersión publicada
000070603 8564_ $$s125827$$uhttps://zaguan.unizar.es/record/70603/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000070603 909CO $$ooai:zaguan.unizar.es:70603$$particulos$$pdriver
000070603 951__ $$a2020-02-21-13:48:51
000070603 980__ $$aARTICLE