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B chronic lymphocytic leukemia cell interleukin production involves RANKL/RANK

06-02-2006

According to a study from Italy, B chronic lymphocytic leukemia (B-CLL) cell interleukin (IL) production involves RANKL/RANK.

"B-CLL cells express several members of the tumor necrosis factor (TNF) family, such as CD40L, CD30L, and TRAIL. By using the cDNA microarray technology, B-CLL samples were found to overexpress receptor activator of nuclear factor kB (NF-kB) ligand (RANKL), as compared to normal CD19+ B cells," wrote P. Secchiero and colleagues, University of Ferrara.

"These findings were validated at the protein level by Western blot and flow cytometry analyses. Moreover, unlike primary normal B cells, leukemic B-CLL cells showed surface expression of RANK, the cognate transmembrane receptor of RANKL.

"When added in vitro to B-CLL cultures, either alone or in association with chlorambucil or fludarabine, recombinant RANKL did not significantly modulate cell viability, and it minimally affected the IL-8 expression/release. On the other hand, treatment with RANK-Fc chimera potently upregulated the release of IL-8 in the B-CLL culture supernatants, suggesting involvement of reverse signaling through transmembrane RANKL in IL-8 induction," the authors reported.

"In turn, exposure of B-CLL cells to recombinant IL-8 significantly decreased spontaneous apoptosis as well as chlorambucil- and fludarabine-mediated cytotoxicity in B-CLL cells," Secchiero and coinvestigators continued.

They concluded, "Since IL-8 has been implicated in progression of B-CLL disease, our findings suggest that, by upregulating IL-8, the RANKL/RANK system may contribute to the pathogenesis of B-CLL."

Secchiero and colleagues published their study in the Journal of Cellular Physiology (Role of the RANKL/RANK system in the induction of interleukin-8 (IL-8) in B chronic lymphocytic leukemia (B-CLL) cells. J Cell Physiol, 2006;207(1):158-164).

For more information, contact P. Secchiero, University of Ferrara, Human Anatomy Section, Department of Morphology & Embryology, Via Fossato Mortara 66, I-44100 Ferrara, Italy.

Publisher contact information for the Journal of Cellular Physiology is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Keywords: Ferrara, Italy, Apoptosis, Chlorambucil, DNA Microarrays, B Chronic Lymphocytic Leukemia, Nuclear Factors, RANKL/RANK, Interleukin.

This article was prepared by Cancer Weekly editors from staff and other reports. Copyright 2006, Cancer Weekly via NewsRx.com.