Bone marrow stroma CD40 expression correlates with inflammatory mast cell infiltration and disease progression in splenic marginal zone lymphoma

Alessandro Gulino, Carla Guarnotta, Rossana Porcasi, Ada Maria Florena, Vito Franco, Claudio Tripodo, Giovanni Franco, Elena Betto, Alice Rigoni, Stefano Aldo Pileri, Fabio Fuligni, Sabina Sangaletti, Barbara Frossi, Emanuela Boveri, Luca Arcaini, Pier Paolo Piccaluga, Carlo Pucillo, Mario Paolo Colombo

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

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 genetics and the 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.
Original languageEnglish
Pages (from-to)1836-1849
Number of pages14
JournalBlood
Volume123
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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