CD20 and CD40 mediated mitogenic responses in B‐lineage acute lymphoblastic leukaemia

Abstract

Activation of CD20, a cross-membrane ion channel, induces cell cycle progression from G0 to G1 in B lymphocytes. Subsequent activation of CD40, a membrane receptor of the nerve growth factor receptor superfamily, transits the B cells to the S phase. CD40 may also act synergistically in combination with IL-4 (B lymphocytes) or IL-3/IL-7 (B-cell precursors). We investigated the proliferative responses of B-lineage acute lymphoblastic leukaemia (ALL) cells to CD20/CD40 activation. In 18/56 ALL cases, CD20 activation resulted in significant increases in DNA synthesis. Similar, although more moderate, effects were seen of activation of CD40 in 10/44 cases. Responses to CD20 or CD40 activation were independent of co-stimulation with IL-3, IL-4 or IL-7, and various cocktails of the different growth stimuli did not act synergistically.

The Power of Monoclonal Antibodies as Agents of Discovery: CD40 Revealed as a B Lymphocyte Costimulator

“…CD40 prestimulation enhances the death of chronic lymphocyte leukemia cells induced by anti-CD20 mAbs (27), and simultaneous delivery of CD40 1 CD20 signals enhances the in vitro proliferation inhibition of transformed human B cell lines and non-Hodgkin lymphoma cells (28). However, prestimulation of CD20 was found to enhance the proliferative response of B cell acute lymphoblastic leukemia cells to CD40 stimulation (29).…”

Rituximab, Cyclophosphamide, Dexamethasone (RCD) Regimen Induces Cure in WSU-WM Xenograft Model and a Partial Remission in Previously Treated Waldenstrom's Macroglobulinemia Patient

“…When treated with RTX (human mouse anti-CD20 MoAb IDEC-C2B8), tumor responses of up to 50% were observed in patients with low-grade non-Hodgkin's lymphomas (Holder et al, 1995;Shan et al, 1998). The precise mechanism of action of anti-CD20 remains unknown, however, effects of CD20 on resting B-cells indicate that it is able to transduce an extracellular signal affecting G0/G1 phase in the cell cycle (Clark et al, 1982;Golay et al, 1985;Smiers et al, 1995) as well as the activation of tyrosine kinase (Deans et al, 1998).…”