6533b82afe1ef96bd128b783
RESEARCH PRODUCT
Bone marrow stroma CD40 expression correlates with inflammatory mast cell infiltration and disease progression in splenic marginal zone lymphoma
Giovanni FrancoCarla GuarnottaPp PiccalugaE BoveriAlessandro GulinoF FuligniA RigoniR PorcasiS BuffaE BettoAda Maria FlorenaVito FrancoE IannittoL ArcainiSa PileriC PucilloMp ColomboS SangalettiClaudio TripodoB FrossiRossana Porcasisubject
MalePathologyBiochemistryMiceTumor MicroenvironmentMast CellMedicineMast CellsInflammation MediatorAged 80 and overMice KnockoutB-LymphocytesMice Inbred BALB CMesenchymal Stromal CellB-LymphocyteCD40 AntigenCell DifferentiationHematologyMiddle AgedPrognosismedicine.anatomical_structureDisease ProgressionCytokinesFemaleInflammation MediatorsClone (B-cell biology)HumanAdultmedicine.medical_specialtyStromal cellPrognosiCD40 LigandImmunologyDisease-Free SurvivalAnimalsHumansSplenic marginal zone lymphomaCD40 AntigensCytokineB cellAgedCell ProliferationAnimalbusiness.industryMesenchymal stem cellMesenchymal Stem CellsLymphoma B-Cell Marginal ZoneCell BiologyGenes p53medicine.diseaseLymphomaSplenic marginal zone lymphoma bone marrow microenvironment CD40Mast cell sarcomaBone marrowbusinessdescription
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. © 2014 by The American Society of Hematology.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 | Blood |