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dc.contributor.authorReikvam, Håkonen_US
dc.contributor.authorAasebø, Eliseen_US
dc.contributor.authorBrenner, Annetteen_US
dc.contributor.authorBartaula-Brevik, Sushmaen_US
dc.contributor.authorGrønningsæter, Ida Sofieen_US
dc.contributor.authorForthun, Rakel Brendsdalen_US
dc.contributor.authorHovland, Randien_US
dc.contributor.authorBruserud, Øysteinen_US
dc.PublishedReikvam H, Aasebø E, Brenner AK, Bartaula-Brevik S, Grønningsæter IS, Forthun RB, Hovland R, Bruserud Ø. High Constitutive Cytokine Release by Primary Human Acute Myeloid Leukemia Cells Is Associated with a Specific Intercellular Communication Phenotype. Journal of clinical medicine. 2019;8(7):970eng
dc.description.abstractAcute myeloid leukemia (AML) is a heterogeneous disease, and this heterogeneity includes the capacity of constitutive release of extracellular soluble mediators by AML cells. We investigated whether this capacity is associated with molecular genetic abnormalities, and we compared the proteomic profiles of AML cells with high and low release. AML cells were derived from 71 consecutive patients that showed an expected frequency of cytogenetic and molecular genetic abnormalities. The constitutive extracellular release of 34 soluble mediators (CCL and CXCL chemokines, interleukins, proteases, and protease regulators) was investigated for an unselected subset of 62 patients, and they could be classified into high/intermediate/low release subsets based on their general capacity of constitutive secretion. FLT3-ITD was more frequent among patients with high constitutive mediator release, but our present study showed no additional associations between the capacity of constitutive release and 53 other molecular genetic abnormalities. We compared the proteomic profiles of two contrasting patient subsets showing either generally high or low constitutive release. A network analysis among cells with high release levels demonstrated high expression of intracellular proteins interacting with integrins, RAC1, and SYK signaling. In contrast, cells with low release showed high expression of several transcriptional regulators. We conclude that AML cell capacity of constitutive mediator release is characterized by different expression of potential intracellular therapeutic targets.en_US
dc.rightsAttribution CC BYeng
dc.subjectAcute myeloid leukemiaeng
dc.subjectgene mutationseng
dc.subjectproteomic profileeng
dc.titleHigh Constitutive Cytokine Release by Primary Human Acute Myeloid Leukemia Cells Is Associated with a Specific Intercellular Communication Phenotypeen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 The Author(s)
dc.source.journalJournal of clinical medicine

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