TY - JOUR
T1 - Bone marrow stroma CD40 expression correlates with inflammatory mast cell infiltration and disease progression in splenic marginal zone lymphoma
AU - Franco, Giovanni
AU - Guarnotta, Carla
AU - Frossi, Barbara
AU - Piccaluga, Pier Paolo
AU - Boveri, Emanuela
AU - Gulino, Alessandro
AU - Fuligni, Fabio
AU - Rigoni, Alice
AU - Porcasi, Rossana
AU - Buffa, Salvatore
AU - Betto, Elena
AU - Florena, Ada Maria
AU - Franco, Vito
AU - Iannitto, Emilio
AU - Arcaini, Luca
AU - Pileri, Stefano Aldo
AU - Pucillo, Carlo
AU - Colombo, Mario Paolo
AU - Sangaletti, Sabina
AU - Tripodo, Claudio
PY - 2014/3/20
Y1 - 2014/3/20
N2 - Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized by rather indolent clinical course. However, nearly one third of patients experience a rapidly progressive disease with a dismal outcome. Despite the characterization of clone geneticsandthe recognition of deregulated immunologic stimulation in the pathogenesis of SMZL, little is known about microenvironment dynamics and their potential biological influence on disease outcome. Here we investigate the effect of stroma-intrinsic features on SMZL disease progression by focusing on the microenvironment of the bone marrow (BM), which represents an elective disease localization endorsing diagnostic and prognostic relevance. We show that the quality of the BM stromal meshwork of SMZL infiltrates correlates with time to progression. In particular, we describe the unfavorable prognostic influence of dense CD40 expression by BM stromal cells, which involves the contribution of CD40 ligand (CD40L)-expressing bystander mast cells infiltrating SMZL BM aggregates. The CD40/CD40L-assisted crosstalk between mesenchymal stromal cells and mast cells populating the SMZL microenvironment finds correlation in p53-/- mice developing SMZL and contributes to the engendering of detrimental proinflammatory conditions. Our study highlights a dynamic interaction, playing between nonneoplastic elements within the SMZL niche, toward disease progression.
AB - Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized by rather indolent clinical course. However, nearly one third of patients experience a rapidly progressive disease with a dismal outcome. Despite the characterization of clone geneticsandthe recognition of deregulated immunologic stimulation in the pathogenesis of SMZL, little is known about microenvironment dynamics and their potential biological influence on disease outcome. Here we investigate the effect of stroma-intrinsic features on SMZL disease progression by focusing on the microenvironment of the bone marrow (BM), which represents an elective disease localization endorsing diagnostic and prognostic relevance. We show that the quality of the BM stromal meshwork of SMZL infiltrates correlates with time to progression. In particular, we describe the unfavorable prognostic influence of dense CD40 expression by BM stromal cells, which involves the contribution of CD40 ligand (CD40L)-expressing bystander mast cells infiltrating SMZL BM aggregates. The CD40/CD40L-assisted crosstalk between mesenchymal stromal cells and mast cells populating the SMZL microenvironment finds correlation in p53-/- mice developing SMZL and contributes to the engendering of detrimental proinflammatory conditions. Our study highlights a dynamic interaction, playing between nonneoplastic elements within the SMZL niche, toward disease progression.
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U2 - 10.1182/blood-2013-04-497271
DO - 10.1182/blood-2013-04-497271
M3 - Article
C2 - 24452203
AN - SCOPUS:84897512258
VL - 123
SP - 1836
EP - 1849
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -