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dc.contributor.authorBarbier, Sardine
dc.contributor.authorChatre, Laurent
dc.contributor.authorBras, Marlène
dc.contributor.authorSancho, Patricia
dc.contributor.authorRoué, Gaël
dc.contributor.authorVirely, Clémence
dc.contributor.authorYuste Mateos, Víctor J. (Víctor José)
dc.contributor.authorBaudet, Sylvie
dc.contributor.authorRubio, Manuel
dc.contributor.authorEsquerda Colell, Josep
dc.contributor.authorSarfati, Marika
dc.contributor.authorMerle-Béral, Hélène
dc.contributor.authorSusin, Santos A.
dc.date.accessioned2015-12-11T09:57:33Z
dc.date.available2015-12-11T09:57:33Z
dc.date.issued2009
dc.identifier.issn0390-6078
dc.identifier.urihttp://hdl.handle.net/10459.1/49258
dc.description.abstractBackground Programmed cell death has been traditionally related with caspase activation. However, it is now accepted that caspase-independent forms of programmed cell death also regulate cell death. In chronic lymphocytic leukemia, CD47 ligation induces one of these alternative forms of cell death: type III programmed cell death. This poorly understood process is characterized by cytoplasmic hallmarks, such as mitochondrial damage. To gain insights into the molecular pathways regulating type III programmed cell death in chronic lymphocytic leukemia, we performed extensive biochemical and cell biology assessments. Design and Methods After CD47 triggering, purified B-cells from 20 patients with chronic lymphocytic leukemia were studied by flow cytometry, immunofluorescence and three-dimensional imaging, immunoblotting, electron microscopy, and fibrillar/globular actin measurements. Finally, we subjected CD47-treated chronic lymphocytic leukemia cells to a phagocytosis assay. Results We first confirmed that induction of type III programmed cell death is an efficient means of triggering cell death in chronic lymphocytic leukemia. Further, we demonstrated that the signaling events induced by CD47 ligation provoked a reduction in cell size. This alteration is related to F-actin disruption, as the two other cytoskeleton networks, microtubules and intermediate filaments, remain undisturbed in type III programmed cell death. Strikingly, we revealed that the pharmacological modulation of F-actin dynamics regulated this type of death. Finally, our data delineated a new programmed cell death pathway in chronic lymphocytic leukemia initiated by CD47 triggering, and followed by serine protease activation, F-actin rearrangement, mitochondrial damage, phosphatidylserine exposure, and cell clearance. Conclusions Our work reveals a key molecular tool in the modulation of cell death in chronic lymphocytic leukemia: F-actin. By assessing the regulation of F-actin and type III programmed cell death, this analysis provides new options for destroying chronic lymphocytic leukemia cells, such as a combination of therapies based on apoptosis regulators (e.g., caspases, Bcl- 2, Bax) along with alternative therapies based on type III death effectors (e.g., F-actin).ca_ES
dc.language.isoengca_ES
dc.publisherFerrata Storti Foundationca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.3324/haematol.13690ca_ES
dc.relation.ispartofHaematologica, 2009, vol. 94, núm. 4, p. 507-517ca_ES
dc.rights(c) Ferrata Storti Foundation, 2009ca_ES
dc.subjectActinca_ES
dc.subjectApoptosisca_ES
dc.subjectCaspase-independent cell deathca_ES
dc.titleCaspase-independent type III programmed cell death in chronic lymphocytic leukemia: the key role of the F-actin cytoskeletonca_ES
dc.typearticleca_ES
dc.identifier.idgrec015831
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.3324/haematol.13690


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