Revisiting the role of interleukin-8 in chronic lymphocytic leukemia.

The proliferation and survival of malignant B cells in chronic lymphocytic leukemia (CLL) depend on signals from the microenvironment in lymphoid tissues. Among a plethora of soluble factors, IL-8 has been considered one of the most relevant to support CLL B cell progression in an autocrine fashion, even though the expression of IL-8 receptors, CXCR1 and CXCR2, on leukemic B cells has not been reported. Here we show that circulating CLL B cells neither express CXCR1 or CXCR2 nor they respond to exogenous IL-8 when cultured in vitro alone or in the presence of monocytes/nurse-like cells.

The effect of fludarabine on interferon-gamma production by lymphoid cells from healthy donors and patients with B-cell chronic lymphocytic leukemia.

Fludarabine treatment in patients with B-cell chronic lymphocytic leukemia (B-CLL) can trigger or exacerbate the development of autoimmune hemolytic anemia (AHA) through a currently ill-defined mechanism. We here show that exposure of peripheral blood lymphocytes from healthy donors and B-CLL patients to fludarabine increases in vitro production of interferon-gamma, a key cytokine in the pathogenesis of AHA.

In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine.

Administration of the adenosine analogue fludarabine (FLU) in vivo induces a profound and prolonged T lymphopenia which mainly affects CD4(+) cells. To better understand the mechanistic basis underlying this preferential depletion, we analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, our results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8(+) than in CD4(+) T lymphocytes.