期刊
ONCOTARGET
卷 6, 期 39, 页码 42130-42149出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6239
关键词
chronic lymphocytic leukemia; mesenchymal stromal cells; kinase inhibitors
资金
- Ministero dell'Istruzione dell'Universita' e della Ricerca [PRIN 2010-2011]
- Associazione Italiana per la Ricerca sul Cancro AIRC (Milan) (AIRC project ) [15397]
- AIRC Regional Project with Fondazione CARIPARO
- CARIVERONA, Regione Veneto on chronic lymphocytic leukemia
- AIRC (Milan) (AIRC project) [14972]
Leukemic cells from Chronic Lymphocytic Leukemia (CLL) patients interact with stromal cells of the surrounding microenvironment. Mesenchymal Stromal Cells (MSCs) represent the main population in CLL marrow stroma, which may play a key role for disease support and progression. In this study we evaluated whether MSCs influence in vitro CLL cell survival. MSCs were isolated from the bone marrow of 46 CLL patients and were characterized by flow cytometry analysis. Following co-culture of MSCs and leukemic B cells, we demonstrated that MSCs were able to improve leukemic B cell viability, this latter being differently dependent from the signals coming from MSCs. In addition, we found that the co-culture of MSCs with leukemic B cells induced an increased production of IL-8, CCL4, CCL11, and CXCL10 chemokines. As far as drug resistance is concerned, MSCs counteract the cytotoxic effect of Fludarabine/Cyclophosphamide administration in vivo, whereas they do not protect CLL cells from the apoptosis induced by the kinase inhibitors Bafetinib and Ibrutinib. The evidence that leukemic clones are conditioned by environmental stimuli suggest new putative targets for therapy in CLL patients.
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