Transcriptomics,Genomics

Dataset Information

31

Effect of Ibrutinib on the gene expression of CD4+ cells from patients with Peripheral T-cell lymphoma (PTCL)


ABSTRACT: Interleukin-2-inducible T-cell kinase (ITK) has essential roles in T-cell proliferation in response to T-cell receptor stimulation and promotes Th2 and Th17 cell differentiation while suppressing Treg differentiation. ITK inhibitors have not previously been investigated for their ability to modify differentiation of either normal or malignant human CD4+ T-cells. We demonstrate that normal tonsillar CD4+ T-cell differentiation to Tfh and Th17 cells is inhibited by ITK inhibitors (ITKi) while Treg differentiation is promoted. Purified CD4+ T-cells from two cases of peripheral T-cell lymphoma demonstrated the capacity to proliferate and differentiate to Tfh, Th17 or Treg subsets in vitro. Gene expression profiling showed differences in Th-cell signature genes between normal and lymphoma cells. ITKi promoted Treg differentiation while suppressing Tfh and Th17 differentiation. The majority of CD4+ T-cells within lymph node sections did not express BCL6 compatible with the in vitro results being due to differentiation and not outgrowth already differentiated populations. The novel concept suggested by this report is that some cases of PTCL-NOS show a capacity to differentiate, which can be modified by ITKi for potential therapeutic benefit. Overall design: Whole genome gene expression was analysed in normal and lymphoma cells with or without Interleukin-2-inducible T-cell kinase inhibitor

INSTRUMENT(S): Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Feature Number Version]

SUBMITTER: Nicolas Sylvius  

PROVIDER: GSE120403 | GEO | 2018-09-26

REPOSITORIES: GEO

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