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 common but not understood. An explanation may be offered by studying an atypical SLL/CLL case characterized by recurrent cycles of leukemic phase alternating with spontaneous remission (1). During remissions, residual IgMK+ leukemic cells exhibited resting phenotype, low proliferative response to CD40-ligand and delayed apoptosis. In contrast, the acute phase counterparts were phenotypically activated, underwent rapid apoptosis in culture and proliferated extensively in response to membrane-anchored CD40-ligand. Transient bursts of serum TNFa 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 suggest that changes in the lymphoma milieu affect the neoplastic cell activation status, rate of proliferation in response to activated T cells and rate of apoptosis. These responses may underlie both the indu...