Prolymphocytic Leukemia: Malignancy of Activated B Cells with an Apoptosis-like Response to Anti-Human IgM Signal Transduction

Abstract

B-prolymphocytic leukemia (PLL) resembles B-chronic lymphocytic leukemia (CLL) in the expression of surface IgM, but differs in morphology, cellular function, and clinical features, suggesting that PLL and CLL may be derived from distinct B cell subsets in B cell ontogeny. In studies of the signaling effect of anti-human IgM (anti-μ) on B malignancies, the divalent F(ab') anti-μ neither stimulated nor inhibited DNA synthesis of CLL cells but exerted a unique negative signaling effect and direct cytotoxicity on PLL cells in complement-free cultures with morphological cellular changes characteristic of a “programmed cell death” mechanism or apoptosis. The susceptibility of PLL cells to anti-μ-triggered cytotoxicity is similar to the negative signaling effect observed on “tolerogenic” normal B cells. The findings of activated B cell phenotypes in PLL, a high level of autonomous DNA synthesis activity in large “transformed” PLL cells, and mitogen-induced cellular transformation of CLL to PLL indicate that PLL...