Logo do repositório
 
Publicação

On CK2 regulation of chronic lymphocytic leukemia cell viability

2011Artigo científico Acesso restrito
Ver registo simples
dc.contributor.authorMartins, Leila
dc.contributor.authorLúcio, Paulo
dc.contributor.authorSilva, Milene C.
dc.contributor.authorGameiro, Paula
dc.contributor.authorSilva, Maria G.
dc.contributor.authorBarata, João T.
dc.date.accessioned2021-10-20T14:50:25Z
dc.date.available2021-10-20T14:50:25Z
dc.date.issued2011
dc.description© Springer Science+Business Media, LLC. 2011pt_PT
dc.description.abstractSpecific inhibition of signaling elements essential for the viability of B-cell chronic lymphocytic leukemia (CLL) cells offers great promise for the design of more efficient therapies. The protein serine/threonine kinase CK2 is frequently upregulated in cancer, and it is overexpressed and hyperactivated in primary CLL cells from untreated patients. We have shown that inhibition of CK2 induces apoptosis of CLL cells, whereas it does not significantly impact normal lymphocytes, demonstrating the selectivity of the CK2 inhibitors toward leukemia cells. Notably, although co-culture with OP9 stromal cells and BCR stimulation both promote leukemia cell survival in vitro, they do not prevent apoptosis of CLL cells treated with CK2 inhibitors. PI3K signaling pathway was previously shown to be essential for CLL cell viability, an observation we confirmed in all patient samples analyzed. Further, we observed that CK2 blockade decreases PTEN phosphorylation, leading to PTEN activation, and that apoptosis of CLL cells upon CK2 inhibition is mediated by PKC inactivation. This suggests that activation of PI3K/PKC signaling pathway is involved in the pro-survival effects of CK2 in CLL cells. Sensitivity to CK2 inhibition does not correlate with expression of ZAP-70 or CD38, or with IGVH mutation status. However, it positively correlates with the percentage of CLL cells in the peripheral blood, β2 microglobulin levels, and Binet clinical stage. CK2 appears to play an important role in the biology of CLL and constitutes a promising target for the development of leukemia-specific therapies.pt_PT
dc.description.sponsorshipThis study was supported by the grant PIC/IC/83193/2007 from Fundação para a Ciência e a Tecnologia. LRM has an FCT-SFRH PhD fellowship.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMol Cell Biochem. 2011 Oct;356(1-2):51-55pt_PT
dc.identifier.doi10.1007/s11010-011-0947-6pt_PT
dc.identifier.eissn1573-4919
dc.identifier.issn0300-8177
dc.identifier.urihttp://hdl.handle.net/10451/49953
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://www.springer.com/journal/11010/pt_PT
dc.subjectCK2pt_PT
dc.subjectChronic lymphocytic leukemiapt_PT
dc.subjectSignaling therapypt_PT
dc.subjectPI3K-PTENpt_PT
dc.subjectIgMpt_PT
dc.subjectOP9 co-culturept_PT
dc.titleOn CK2 regulation of chronic lymphocytic leukemia cell viabilitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPIC/IC/83193/2007
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F83193%2F2007/PT
oaire.citation.endPage55pt_PT
oaire.citation.issue1-2pt_PT
oaire.citation.startPage51pt_PT
oaire.citation.titleMolecular and Cellular Biochemistrypt_PT
oaire.citation.volume356pt_PT
oaire.fundingStream5646-ICCMS
person.familyNameMartins
person.familyNameBarata
person.givenNameLeila
person.givenNameJoão
person.identifier.orcid0000-0002-5887-4734
person.identifier.orcid0000-0002-4826-8976
person.identifier.ridD-9181-2015
person.identifier.scopus-author-id35901113700
person.identifier.scopus-author-id7006937224
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationb0613657-c454-43f5-b7af-c66b84028d8e
relation.isAuthorOfPublication06f27f7f-1c6c-4c03-a70d-52f8a388bd3b
relation.isAuthorOfPublication.latestForDiscovery06f27f7f-1c6c-4c03-a70d-52f8a388bd3b
relation.isProjectOfPublication5cd47221-105a-45a1-8a98-69616e11037f
relation.isProjectOfPublication.latestForDiscovery5cd47221-105a-45a1-8a98-69616e11037f

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
CK2_regulation.pdf
Tamanho:
279.21 KB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

IMM - Artigos em Revistas Internacionais
FM - Artigos em Revistas Internacionais