E-GEOD-50572 - Gene signature of CLL cells cultured with activated T cells or CD40L-expressing cells
Released on 7 October 2013, last updated on 22 July 2015
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+ 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 production ex vivo 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. CLL cells were cultured under different conditions for 16 hours and then sorted to purity as CD20+ CD5+ cells.
transcription profiling by array
Rogier Versteeg <email@example.com>, E Eldering, F Pascutti
IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells. Pascutti MF, Jak M, Tromp JM, Derks IA, Remmerswaal EB, Thijssen R, van Attekum MH, van Bochove GG, Luijks DM, Pals ST, van Lier RA, Kater AP, van Oers MH, Eldering E.