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Sorafenib targets BCR kinases and blocks migratory and microenvironmental survival signals in CLL cells

Leukemia volume 26, pages 1429–1432 (2012)Cite this article

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of monoclonal B lymphocytes in blood, bone marrow (BM) and secondary lymphoid tissues. The prognosis of the disease is heterogeneous, with no or a low number of somatic hypermutations in the variable region of immunoglobulin genes (IGHV), high expression of ZAP-70 or CD38, and the presence of certain cytogenetic abnormalities, being all associated with poor prognosis.1 Despite the development of more effective treatments, CLL remains incurable with standard therapy.

The multikinase inhibitor sorafenib, which has been approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma, has emerged in the last years as a promising agent for treating tumors in which oncogenic kinases are frequently deregulated.2 Recent studies have shown that CLL cells might be also susceptible to this compound.3, 4 Thus, sorafenib could be particularly relevant in CLL cells by blocking RAF-mediated survival responses in the presence of CXCL12,4 its cytotoxic effect being related to the translational inhibition of the antiapoptotic protein MCL-1.3 In this context, the aim of our study was to investigate the capacity of sorafenib to interfere with B-cell receptor (BCR) signaling and to evaluate its efficacy in modulating migratory and microenvironmental prosurvival signals.

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Acknowledgements

We thank Sandra Cabezas, Laura Jiménez and Jocabed Roldán for their technical support. This work was carried out, in part, at the Esther Koplowitz Center, Barcelona. Sorafenib was kindly provided by Bayer. This work was supported by grants from Ministerio de Ciencia e Innovación (SAF 09/9503), Redes Temáticas de Investigación Cooperativa de Cáncer from the Instituto de Salud Carlos III RED 2006-20-014 (DC), 2006-20-039 (EC) and RED2006-20-059 (EM), Fondo de Investigación Sanitaria (CP07/00072 and PI09/00060) (GR) and Generalitat Catalunya 2009SGR967 (DC). PP-G holds a contract from Ramón y Cajal program (Ministerio de Ciencia e Innovación, RYC2009-05134). SX-T and LR are recipients of predoctoral fellowships from Ministerio de Ciencia e Innovación (FPU) and IDIBAPS, respectively. ML-G and IS-V have a contract from RED 2006-20-014 and RED 2006-20-039, respectively.

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Author notes

  1. M López-Guerra and S Xargay-Torrent: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Hematopathology Unit, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

    M López-Guerra, S Xargay-Torrent, P Pérez-Galán, I Saborit-Villarroya, L Rosich, N Villamor, M Aymerich, G Roué, E Campo & D Colomer

  2. Department of Hematology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

    E Montserrat

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Correspondence to D Colomer.

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López-Guerra, M., Xargay-Torrent, S., Pérez-Galán, P. et al. Sorafenib targets BCR kinases and blocks migratory and microenvironmental survival signals in CLL cells. Leukemia 26, 1429–1432 (2012). https://doi.org/10.1038/leu.2011.364

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