IL-4 enhances expression and function of surface IgM in CLL cells.

摘要: Kinase inhibitors targeting the B-cell receptor (BCR) are now prominent in treatment of chronic lymphocytic leukemia (CLL). We have focused here on interleukin 4 (IL-4), a cytokine that protects normal and malignant B cells from apoptosis increases surface immunoglobulin M (sIgM) expression murine splenic cells. First, we demonstrated IL-4 increased sIgM vitro peripheral blood obtained healthy individuals. In CLL, target genes overexpressed purified lymph nodes patients compared with derived matched bone marrow samples. As for cells, CLL vitro, especially samples expressing unmutated V-genes. IL-4-induced was associated signalling activity, measured by anti-IgM-induced calcium mobilization, CD79B messenger RNA protein, "mature" glycoform sIgM. Importantly, ability BCR-associated kinase idelalisib ibrutinib, approved other malignancies, to inhibit reduced following pretreatment majority patients. contrast stimulatory effects sIgM, decreased CXCR4 CXCR5 expression; therefore, particularly within progressive V-gene subset, may harness promote BCR retention nodes. Effects were mediated via JAK3/STAT6 propose potential role JAK combination CLL.