Neoplastic cell activation and proliferative response to CD40-ligand characterize recurrent leukemic bouts in an unusual case of low grade lymphoma

Spontaneous fluctuations in activity of low-grade B cell lymphomas are comm on but not understood. An explanation may be offered by studying an atypica l SLL/CLL case characterized by recurrent cycles of leukemic phase alternat ing with spontaneous remission (1). During remissions, residual IgM kappa() leukemic cells exhibited resting phenotype, low proliferative response to CD40-ligand and delayed apoptosis. In contrast, the acute phase counterpar ts were phenotypically activated, underwent rapid apoptosis in culture and proliferated extensively in response to membrane-anchored CD40-ligand. Tran sient bursts of serum TNF alpha and IL-10 preceded the acute phases, which were characterized by the co-existence of CD40-ligand(+) T lymphocytes and lymphoma cells in the bone marrow Based on ex-vivo and in-vitro data, we su ggest that changes in the lymphoma milieu affect the neoplastic cell activa tion status, rate of proliferation in response to activated T cells and rat e of apoptosis. These responses may underlie both the induction and spontan eous regression of the acute phases in this unique lymphoma. Our findings r aise the possibility that part of this mechanism may have evolved during tr ansformation of indolent common CLL to its more aggressive form.