Aberrant Expression of Functional BAFF-System Receptors by Malignant B-Cell Precursors Impacts Leukemia Cell Survival

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Aberrant Expression of Functional BAFF-System Receptors by Malignant B-Cell Precursors Impacts Leukemia Cell Survival

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dc.contributor.author Maia, Sara
dc.contributor.author Pelletier, Marc
dc.contributor.author Ding, Jixin
dc.contributor.author Hsu, Yen-Ming
dc.contributor.author Rao, Sambasiva P.
dc.contributor.author Cardoso, Angelo A.
dc.contributor.author Sallan, Stephen Earl
dc.contributor.author Nadler, Lee Marshall
dc.date.accessioned 2011-12-29T05:38:11Z
dc.date.issued 2011
dc.identifier.citation Maia, Sara, Marc Pelletier, Jixin Ding, Yen-Ming Hsu, Stephen E. Sallan, Sambasiva P. Rao, Lee M. Nadler, and Angelo A. Cardoso. 2011. Aberrant expression of functional BAFF-System receptors by Malignant B-cell precursors impacts leukemia cell survival. PLoS ONE 6(6): e20787. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978698
dc.description.abstract Despite exhibiting oncogenic events, patient's leukemia cells are responsive and dependent on signals from their malignant bone marrow (BM) microenvironment, which modulate their survival, cell cycle progression, trafficking and resistance to chemotherapy. Identification of the signaling pathways mediating this leukemia/microenvironment interplay is critical for the development of novel molecular targeted therapies. We observed that primary leukemia B-cell precursors aberrantly express receptors of the BAFF-system, BAFF-R, BCMA, and TACI. These receptors are functional as their ligation triggers activation of NF-kB, MAPK/JNK, and Akt signaling. Leukemia cells express surface BAFF and APRIL ligands, and soluble BAFF is significantly higher in leukemia patients in comparison to age-matched controls. Interestingly, leukemia cells also express surface APRIL, which seems to be encoded by APRIL-\(\delta\), a novel isoform that lacks the furin convertase domain. Importantly, we observed BM microenvironmental cells express the ligands BAFF and APRIL, including surface and secreted BAFF by BM endothelial cells. Functional studies showed that signals through BAFF-system receptors impact the survival and basal proliferation of leukemia B-cell precursors, and support the involvement of both homotypic and heterotypic mechanisms. This study shows an unforeseen role for the BAFF-system in the biology of precursor B-cell leukemia, and suggests that the target disruption of BAFF signals may constitute a valid strategy for the treatment of this cancer. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0020787 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110793/pdf/ en_US
dash.license LAA
dc.subject biology en_US
dc.subject molecular cell biology en_US
dc.subject cytometry en_US
dc.subject flow cytometry en_US
dc.subject medicine en_US
dc.subject hematology en_US
dc.subject hematologic cancers and related disorders en_US
dc.subject basic cancer research en_US
dc.subject oncology en_US
dc.title Aberrant Expression of Functional BAFF-System Receptors by Malignant B-Cell Precursors Impacts Leukemia Cell Survival en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Nadler, Lee Marshall
dc.date.available 2011-12-29T05:38:11Z
dash.affiliation.other 100174 en_US
dash.affiliation.other 103305 en_US
dash.affiliation.other 100178 en_US

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