Revisiting the role of interleukin-8 in chronic lymphocytic leukemia

PODAZA, ENRIQUE; ELÍAS, ESTEBAN ENRIQUE; BORGE, MERCEDES; RISNIK, DENISE; COLADO, ANA; FERNÁNDEZ GRECCO, HORACIO; GIORDANO, MIRTA; ALMEJÚN, MARÍA BELÉN; BEZARES, RAIMUNDO FERNANDO; GAMBERALE, ROMINA

Buenos Aires

Congreso; Reunión conjunta de sociedades de biociencia; 2017

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. The purpose of this work was to re-examine the role of IL-8 in CLL evaluating the expression of IL-8 receptors in leukemic cells and their capacity to produce IL-8. To this aim we studied samples from patients at different stages of the disease and belonging to different risk groups according to IgVH mutational status, CD38 and CD49d expression levels. Our results show that CLL B cells, resting or activated through their B cell receptor, do not express CXCR1 or CXCR2 (analysis was performed by flow cytometry using neutrophils as positive control, n=39). In accordance to these, CLL cells did not show increased cell survival in response to exogenous IL-8 when cultured in vitro alone or in the presence of monocytes/nurse like cells (n=9). We next determined if CLL B cells were able to produce IL-8. To this end, peripheral blood mononuclear cells (PBMC) were activated with anti-IgM plus CD40 ligand for 24-72 hs and IL-8 production was assessed by flow cytometry (n=17). We found that CLL B cells (CD19+) do not produce IL-8 spontaneously or upon activation, while monocytes (CD14+ cells) did. Therefore, we compared by ELISA, the capacity of PBMC and highly purified CLL cells to release IL-8. We found that a minor proportion of monocytes (PBMC: 0.82% versus purified CLL-B cells: 0.03%) was responsible for IL-8 levels in supernatants (1.178 ± 544 pg/ml versus 42 ± 20 pg/ml, n=13 p