Co-culture of primary CLL cells with bone marrow mesenchymal cells, CD40 ligand and CpG ODN promotes proliferation of chemoresistant CLL cells phenotypically comparable to those proliferating in vivo
Purroy i Zuriguel, Noèlia (Hospital Universitari Vall d'Hebron)
Abrisqueta, Pau (Hospital Universitari Vall d'Hebron)
Carabia, Júlia (Hospital Universitari Vall d'Hebron)
Carpio Segura, Cecilia del Carmen (Hospital Universitari Vall d'Hebron)
Palacio-García, Carles (Hospital Universitari Vall d'Hebron)
Bosch Albareda, Francesc 1947- (Hospital Universitari Vall d'Hebron)
Crespo Maull, Marta (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Data:	2014
Resum:	Chronic lymphocytic leukemia (CLL) cells residing in the bone marrow (BM) and in secondary lymphoid tissues receive survival and proliferative signals from the microenvironment, resulting in persistence of residual disease after treatment. In this study, we characterized primary CLL cells cultured with BM stromal cells, CD40 ligand and CpG ODN to partially mimic the microenvironment in the proliferative centers. This co-culture system induced proliferation and chemoresistance in primary CLL cells. Importantly, co-cultured primary CLL cells shared many phenotypical features with circulating proliferative CLL cells, such as upregulation of ZAP-70 and CD38 and higher CD49d and CD62L expression. This indicates aggressiveness and capability to interact with surrounding cells, respectively. In addition, levels of CXCR4 were decreased due to CXCR4 internalization after CXCL12 stimulation by BM stromal cells. We suggest that this co-culture system can be used to test drugs and their combinations that target the proliferative and drug resistant CLL cells.
Ajuts:	Instituto de Salud Carlos III PI11-00792
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	CLL ; Co-culture ; Proliferation ; Immunophenotype ; Chemoresistance ; ZAP-70
Publicat a:	Oncotarget, Vol. 6 (december 2014) , p. 7632-7643, ISSN 1949-2553

PMID: 25544766

12 p, 3.3 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats