Distinction between asymptomatic monoclonal b-cell lymphocytosis with cyclin d1 overexpression and mantle cell lymphoma: From molecular profiling to flow cytometry

Blanca Espinet, Ana Ferrer, Beatriz Bellosillo, Lara Nonell, Antonio Salar, Concepcion Fernandez-Rodriguez, Eulalia Puigdecanet, Javier Gimeno, Mar Garcia-Garcia, Maria Carmen Vela, Elisa Luno, Rosa Collado, Jose Tomas Navarro, Esmeralda De La Banda, Pau Abrisqueta, Leonor Arenillas, Cristina Serrano, Josep Lloreta, Belen Minana, Andrea CeruttiLourdes Florensa, Alberto Orfao, Ferran Sanz, Francesc Sole, David Dominguez-Sola, Sergio Serrano

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35 Citations (Scopus)


Purpose: 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 24MCLand 13MALD1cases 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 betweenMCLandMALD1and 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. © 2014 American Association for Cancer Research.
Original languageEnglish
Pages (from-to)1007-1019
JournalClinical Cancer Research
Issue number4
Publication statusPublished - 1 Jan 2014


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