000147816 001__ 147816 000147816 005__ 20250109150035.0 000147816 0247_ $$2doi$$a10.1158/1078-0432.ccr-13-1077 000147816 0248_ $$2sideral$$a129723 000147816 037__ $$aART-2014-129723 000147816 041__ $$aeng 000147816 100__ $$aEspinet, Blanca 000147816 245__ $$aDistinction between Asymptomatic Monoclonal B-cell Lymphocytosis with Cyclin D1 Overexpression and Mantle Cell Lymphoma: From Molecular Profiling to Flow Cytometry 000147816 260__ $$c2014 000147816 5060_ $$aAccess copy available to the general public$$fUnrestricted 000147816 5203_ $$aPurpose: According to current diagnostic criteria, mantle cell lymphoma (MCL) encompasses the usual, aggressive variants and rare, nonnodal cases with monoclonal asymptomatic lymphocytosis, cyclin D1–positive (MALD1). We aimed to understand the biology behind this clinical heterogeneity and to identify markers for adequate identification of MALD1 cases. Experimental Design: We compared 17 typical MCL cases with a homogeneous group of 13 untreated MALD1 cases (median follow-up, 71 months). We conducted gene expression profiling with functional analysis in five MCL and five MALD1. Results were validated in 12 MCL and 8 MALD1 additional cases by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in 24 MCL and 13 MALD1 cases by flow cytometry. Classification and regression trees strategy was used to generate an algorithm based on CD38 and CD200 expression by flow cytometry. Results: We found 171 differentially expressed genes with enrichment of neoplastic behavior and cell proliferation signatures in MCL. Conversely, MALD1 was enriched in gene sets related to immune activation and inflammatory responses. CD38 and CD200 were differentially expressed between MCL and MALD1 and confirmed by flow cytometry (median CD38, 89% vs. 14%; median CD200, 0% vs. 24%, respectively). Assessment of both proteins allowed classifying 85% (11 of 13) of MALD1 cases whereas 15% remained unclassified. SOX11 expression by qRT-PCR was significantly different between MCL and MALD1 groups but did not improve the classification. Conclusion: We show for the first time that MALD1, in contrast to MCL, is characterized by immune activation and driven by inflammatory cues. Assessment of CD38/CD200 by flow cytometry is useful to distinguish most cases of MALD1 from MCL in the clinical setting. MALD1 should be identified and segregated from the current MCL category to avoid overdiagnosis and unnecessary treatment 000147816 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000147816 590__ $$a8.722$$b2014 000147816 591__ $$aONCOLOGY$$b12 / 209 = 0.057$$c2014$$dQ1$$eT1 000147816 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000147816 700__ $$aFerrer, Ana 000147816 700__ $$aBellosillo, Beatriz 000147816 700__ $$aNonell, Lara 000147816 700__ $$aSalar, Antonio 000147816 700__ $$aFernández-Rodríguez, Concepción 000147816 700__ $$aPuigdecanet, Eul\u00e0lia 000147816 700__ $$aGimeno, Javier 000147816 700__ $$0(orcid)0000-0003-2078-8205$$aGarcia-Garcia, Mar 000147816 700__ $$aVela, Maria Carmen 000147816 700__ $$aLuño, Elisa 000147816 700__ $$aCollado, Rosa 000147816 700__ $$aNavarro, José Tomás 000147816 700__ $$ade la Banda, Esmeralda 000147816 700__ $$aAbrisqueta, Pau 000147816 700__ $$aArenillas, Leonor 000147816 700__ $$aSerrano, Cristina 000147816 700__ $$aLloreta, Josep 000147816 700__ $$aMiñana, Belén 000147816 700__ $$aCerutti, Andrea 000147816 700__ $$aFlorensa, Lourdes 000147816 700__ $$aOrfao, Alberto 000147816 700__ $$aSanz, Ferran 000147816 700__ $$aSolé, Francesc 000147816 700__ $$aDominguez-Sola, David 000147816 700__ $$aSerrano, Sergio 000147816 773__ $$g20, 4 (2014), 1007-1019$$pClin. cancer res.$$tCLINICAL CANCER RESEARCH$$x1078-0432 000147816 8564_ $$s256310$$uhttps://zaguan.unizar.es/record/147816/files/texto_completo.pdf$$yPostprint 000147816 8564_ $$s1452383$$uhttps://zaguan.unizar.es/record/147816/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000147816 909CO $$ooai:zaguan.unizar.es:147816$$particulos$$pdriver 000147816 951__ $$a2025-01-09-14:59:03 000147816 980__ $$aARTICLE