title: Neoplastic cell activation and proliferative response to CD40-ligand characterize recurrent leukemic bouts in an unusual case of low grade lymphoma.
abstract: 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 IgMkappa+ leukemic cells exhibited resting phenotype, low proliferative response to CD4O-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 TNFalpha 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 induction and spontaneous regression of the acute phases in this unique lymphoma. Our findings raise the possibility that part of this mechanism may have evolved during transformation of indolent common CLL to its more aggressive form.
authors.affiliation: Institute of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Aizman
authors.forename: A
authors.initials: A
authors.lastname: Many
authors.forename: E
authors.initials: E
authors.lastname: Rosenthal
authors.forename: G
authors.initials: G
authors.lastname: Schiby
authors.forename: I
authors.initials: I
authors.lastname: Goldberg
authors.forename: V
authors.initials: V
authors.lastname: Barak
authors.forename: B
authors.initials: B
authors.lastname: Ramot
authors.forename: Y
authors.initials: Y
authors.lastname: Kaufmann
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D023201:CD40 Ligand; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D012008:Recurrence; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; D019014:fas Receptor; D023201:CD40 Ligand