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E-GEOD-50572

ABSTRACT: Gene signature of CLL cells cultured with activated T cells or CD40L-expressing cells

OTHER RELATED OMICS DATASETS IN: PRJNA217965

PROVIDER: E-GEOD-50572 | ExpressionAtlas | 2025-01-24

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-GEOD-50572-analysis-methods.tsv	Tabular
	E-GEOD-50572-atlasExperimentSummary.Rdata	Rdata
	E-GEOD-50572-configuration.xml	Xml
	E-GEOD-50572-percentile-ranks.tsv	Tabular
	E-GEOD-50572.condensed-sdrf.tsv	Tabular

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Project description:NOTCH1 is mutationally activated in ~15% of cases of chronic lymphocytic leukaemia (CLL), but its role in B-cell development and leukemogenesis is not known. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ~50% of peripheral blood CLL cases lacking gene mutations. We identify a ‘NOTCH1 CLL gene expression signature’ in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival and signal transduction physiology. In particular, we show that MYC is a direct target of NOTCH1 via B-cell specific distal regulatory elements, thus implicating this oncogene in the pathogenesis of the disease.

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Gene signature of CLL cells cultured with activated T cells or CD40L-expressing cells

Project description:Chronic Lymphocytic Leukemia (CLL) cells multiply in secondary lymphoid tissue but the mechanisms leading to their proliferation are still uncertain. In addition to BCR-triggered signals, other microenvironmental factors might well be involved. In proliferation centres, leukemic B cells are in close contact with CD4+CD40L+Â T cells. Therefore, we here dissected the signals provided by autologous activated T cells (Tact) to CLL cells. Although the gene expression profile induced by Tact was highly similar to that induced by sole CD40 signaling, an obvious difference was that Tact induced proliferation of CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to induce robust proliferation in CLL cells. We then defined an IL-21-induced gene signature in CLL, containing components of JAK-STAT and apoptosis pathways, and this signature could be detected in lymph node (LN) samples from patients. Finally, we could detect IL-21 RNA and protein in LN, and IL-21 productionÂ ex vivoÂ by LN CD4+CXCR5+ follicular helper T cells. These results indicate that, in addition to BCR signaling, activated T cells might contribute to CLL cell proliferation via CD40 and IL-21. Targeting these signaling pathways might offer new venues for treatment of CLL.Â CLL cells were cultured under different conditions for 16 hours and then sorted to purity as CD20+ CD5+ cells.

2013-10-07 | E-GEOD-50572 | biostudies-arrayexpress

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