TY - JOUR
T1 - Distinction between asymptomatic monoclonal b-cell lymphocytosis with cyclin d1 overexpression and mantle cell lymphoma: From molecular profiling to flow cytometry
AU - Espinet, Blanca
AU - Ferrer, Ana
AU - Bellosillo, Beatriz
AU - Nonell, Lara
AU - Salar, Antonio
AU - Fernandez-Rodriguez, Concepcion
AU - Puigdecanet, Eulalia
AU - Gimeno, Javier
AU - Garcia-Garcia, Mar
AU - Carmen Vela, Maria
AU - Luno, Elisa
AU - Collado, Rosa
AU - Navarro, Jose Tomas
AU - De La Banda, Esmeralda
AU - Abrisqueta, Pau
AU - Arenillas, Leonor
AU - Serrano, Cristina
AU - Lloreta, Josep
AU - Minana, Belen
AU - Cerutti, Andrea
AU - Florensa, Lourdes
AU - Orfao, Alberto
AU - Sanz, Ferran
AU - Sole, Francesc
AU - Dominguez-Sola, David
AU - Serrano, Sergio
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
U2 - 10.1158/1078-0432.CCR-13-1077
DO - 10.1158/1078-0432.CCR-13-1077
M3 - Article
SN - 1078-0432
VL - 20
SP - 1007
EP - 1019
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -
