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dc.contributor.authorBlix, Egil Støre
dc.contributor.authorIrish, Jonathan M.
dc.contributor.authorHusebekk, Anne
dc.contributor.authorDelabie, Jan
dc.contributor.authorForfang, Lise
dc.contributor.authorTierens, Anne
dc.contributor.authorMyklebust, June
dc.contributor.authorKolstad, Arne
dc.date.accessioned2013-03-13T12:39:02Z
dc.date.available2013-03-13T12:39:02Z
dc.date.issued2012
dc.description.abstractKnowledge about signaling pathways in malignant cells may provide prognostic and diagnostic information in addition to identify potential molecular targets for therapy. B-cell receptor (BCR) and co-receptor CD40 signaling is essential for normal B cells, and there is increasing evidence that signaling via BCR and CD40 plays an important role in the pathogenesis of B-cell lymphoma. The aim of this study was to investigate basal and induced signaling in lymphoma B cells and infiltrating T cells in single-cell suspensions of biopsies from small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and marginal zone lymphoma (MZL) patients. Samples from untreated SLL/CLL and MZL patients were examined for basal and activation induced signaling by phospho-specific flow cytometry. A panel of 9 stimulation conditions targeting B and T cells, including crosslinking of the B cell receptor (BCR), CD40 ligand and interleukins in combination with 12 matching phospho-protein readouts was used to study signaling. Malignant B cells from SLL/CLL patients had higher basal levels of phosphorylated (p)-SFKs, p-PLCγ, p-ERK, p-p38, p-p65 (NF-κB), p-STAT5 and p-STAT6, compared to healthy donor B cells. In contrast, anti-BCR induced signaling was highly impaired in SLL/CLL and MZL B cells as determined by low p-SFK, p-SYK and p-PLCγ levels. Impaired anti-BCR-induced p-PLCγ was associated with reduced surface expression of IgM and CD79b. Similarly, CD40L-induced p-ERK and p-p38 were also significantly reduced in lymphoma B cells, whereas p-p65 (NF-κB) was equal to that of normal B cells. In contrast, IL-2, IL-7 and IL-15 induced p-STAT5 in tumor-infiltrating T cells were not different from normal T cells. BCR signaling and CD40L-induced p-p38 was suppressed in malignant B cells from SLL/CLL and MZL patients. Single-cell phospho-specific flow cytometry for detection of basal as well as activation-induced phosphorylation of signaling proteins in distinct cell populations can be used to identify aberrant signaling pathways.en
dc.descriptionThis paper is part of Egil Støre Blix' ph.d thesis which is available in Munin at <a href=http://hdl.handle.net/10037/7755>http://hdl.handle.net/10037/7755</a>en
dc.identifier.citationBMC Cancer (2012), vol. 12 (478)en
dc.identifier.cristinIDFRIDAID 999685
dc.identifier.doihttp://dx.doi.org/10.1186/1471-2407-12-478
dc.identifier.issn1471-2407
dc.identifier.urihttps://hdl.handle.net/10037/4997
dc.identifier.urnURN:NBN:no-uit_munin_4675
dc.language.isoengen
dc.publisherBioMed Centralen
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical molecular biology: 711en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711en
dc.titlePhospho-spesific flow cytometry identifies aberrant signaling in indolent B-cell lymphomaen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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