Fc Receptor–like Proteins (FCRL): Immunomodulators of B Cell Function

“…These genes belong to a large family of lymphocyte receptors with immunoreceptor tyrosine-based inhibition motifs (ITIM). 28,29 These ITIMs can be phosphorylated following external stimuli and can subsequently recruit phosphatases. They can therefore have an inhibitory role in BCR 30 or in MAPK signaling.…”

Section: Cd38mentioning

confidence: 99%

Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA

Stamatopoulos¹,

Haibe‐Kains²,

Equeter³

et al. 2009

Haematologica

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The online version of this article contains a supplementary appendix.Background Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia, but mechanisms by which its higher expression leads to a poor outcome must still be fully explained. Design and MethodsIn an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B cells from chronic lymphocytic leukemia patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Two groups of 7 patients were compared, selected on the basis of either high or low ZAP70 mRNA expression. ResultsTwenty-seven genes were differentially expressed with an FDR<10%, and several genes were significant predictors of treatment-free survival (TFS) and/or overall survival; PDE8A and FCRL family genes (down-regulated in ZAP70 + patients) could predict TFS and overall survival; ITGA4 mRNA (up-regulated in ZAP70 + patients) could significantly predict overall survival. Importantly, gene set enrichment analysis revealed overrepresentation of adhesion/migration genes. We therefore investigated in vitro adhesion/migration capacity of chronic lymphocytic leukemia cells into a stromal microenvironment or in response to conditioned medium. We showed that ZAP70 + cells had better adhesion/migration capacities and only ZAP70 + patient cells responded to microenvironment contact by CXCR4 downregulation. ConclusionsWe concluded that several prognostic factors are the reflection of microenvironment interactions and that the increased adhesion/migratory capacity of ZAP70 + cells in their microenvironment can explain their better survival and thus the aggressiveness of the disease.Key words: chronic lymphocytic leukemia, ZAP70, microarrays, microenvironment, prognosis.Citation: Stamatopoulos B, Haibe-Kains B, Equeter C, Meuleman N, Sorée A, De Bruyn C, Hanosset D, Bron D, Martiat P, and Lagneaux L. Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA. Haematologica 2009; 94:790-799. doi:10.3324/haematol.2008 This is an open-access paper.Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA

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“…Capital letters were added to FcR names to designate human genes and their murine orthologs. More recently, a novel family of FcR-like (FCRL) molecules was disclosed in mice and humans, which dramatically expanded the FcR field (Ehrhardt et al 2007). Many FCRLs still have no known ligand.…”

Section: Prefacementioning

confidence: 99%

Fc Receptors

2014

Current Topics in Microbiology and Immunology

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Fc Receptor–like Proteins (FCRL): Immunomodulators of B Cell Function

Cited by 37 publications

References 40 publications

Circulating CD21^lowB cells in common variable immunodeficiency resemble tissue homing, innate-like B cells

Circulating CD21^lowB cells in common variable immunodeficiency resemble tissue homing, innate-like B cells

Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA

Fc Receptors

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Fc Receptor–like Proteins (FCRL): Immunomodulators of B Cell Function

Cited by 37 publications

References 40 publications

Circulating CD21lowB cells in common variable immunodeficiency resemble tissue homing, innate-like B cells

Circulating CD21lowB cells in common variable immunodeficiency resemble tissue homing, innate-like B cells

Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA

Fc Receptors

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Product

Resources

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Circulating CD21^lowB cells in common variable immunodeficiency resemble tissue homing, innate-like B cells

Circulating CD21^lowB cells in common variable immunodeficiency resemble tissue homing, innate-like B cells