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In contrast to high CD49d, low CXCR4 expression indicates the dependency of chronic lymphocytic leukemia (CLL) cells on the microenvironment

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Abstract

CD49d and CXCR4 are key determinants of interactions between chronic lymphocytic leukemia (CLL) tumor cells and their microenvironment. In this study, we investigated the effect of CD49d and CXCR4 expressions on survival of CLL cells. Primary CLL cells were cultured with CD49d ligand, VCAM-1, or bone marrow stromal cells (BMSCs); then, apoptosis and immunophenotype analyses were performed. VCAM-1 treatment could not induce direct apoptosis protection or immunophenotype change on the CD49d-expressing CLL cells, but resulted in actin reorganization. The BMSC-induced apoptosis protection was independent from the presence of CD49d expression of CLL cells, but showed an inverse correlation with their CXCR4 expression level. We suppose that CD49d contributes to enhanced survival of leukemic cells by mediating migration to the protective microenvironment, not by direct prevention of apoptosis. Moreover, CLL cells with low CXCR4 expression represent a subpopulation that is more dependent on the microenvironmental stimuli for survival, and show increased “death by neglect” when separated from the supportive niche.

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Acknowledgements

The authors would like to thank O. Szabó for contributing to this study with flow cytometric analysis.

Funding

This work was supported by grants from the Hungarian Scientific Research Foundation OTKA (K84262), the NVKP_16-1-2016-0004 grant of the Hungarian National Research, Development and Innovation Office (NFKIH), and the PhD fellowship granted by the Semmelweis University, Budapest.

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Authors and Affiliations

  1. 1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, H-1085 Üllői út 26, Budapest, Hungary

    Csilla Kriston, Ágnes Márk, Anna Sebestyén, Edina Bugyik, András Matolcsy & Gábor Barna

  2. Department of Hematology, Markusovszky University Teaching Hospital, Szombathely, Hungary

    Márk Plander

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  1. Csilla Kriston
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Kriston, C., Plander, M., Márk, Á. et al. In contrast to high CD49d, low CXCR4 expression indicates the dependency of chronic lymphocytic leukemia (CLL) cells on the microenvironment. Ann Hematol 97, 2145–2152 (2018). https://doi.org/10.1007/s00277-018-3410-x

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  • DOI: https://doi.org/10.1007/s00277-018-3410-x

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