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Stromal cell-induced miRNA alteration in chronic lymphocytic leukemia: how a minute and unavoidable cell contamination impairs miRNA profiling

Leukemia volume 27, pages 1773–1776 (2013)Cite this article

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Chronic lymphocytic leukemia (CLL) is characterized by the accumulation in the blood and the primary lymphoid organs of long-lasting, mature, but non-functional B lymphocytes. Interactions of leukemic cells with the microenvironment are known to be critical for CLL cell survival in vivo.1 Indeed, CLL cells can survive for long time periods in vivo while cells are undergoing apoptosis quickly in vitro. This spontaneous apoptosis and the sensitivity of CLL cells to drugs observed in vitro are strongly reduced in the presence of stromal cells,2, 3, 4, 5 which provide stimuli to CLL cells mainly via direct contact. Mimicking in vivo conditions to investigate the mechanisms involved in CLL resistance thus requires the setup of coculture systems. MicroRNAs (miRNA) represent important regulators of gene expression and contribute to CLL pathology.6, 7, 8 Recently, an extensive alteration of miRNA levels in CLL cells was reported after direct culture on stromal cells.9, 10

To investigate the possible transfer of miRNAs from stromal cells to CLL cells through extracellular vesicles13 or through gap junctional intercellular communication (GJIC),14 CLL and stromal cells were cocultured separated by a membrane (0.4 μm pores, Transwell, Corning, Amsterdam, The Netherlands) or in the presence of the GJIC inhibitor 1-octanol (0.5 μM, Sigma, Diegem, Belgium). We observed that the membrane abolished the miR-99a and miR-125b level increase in CLL cells, while the GJIC inhibitor did not exhibit any effect (data not shown). These results rule out the transfer of these miRNAs from stromal to CLL cells by extracellular vesicles or GJIC.

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Acknowledgements

This work was supported by grants from Fonds National de la Recherche Luxembourg to EM and Télévie to JP. We thank Drs E Viry and B Janji and Professor R Bjerkvig at CRP-Santé for their helpful discussions and critical reading of the manuscript.

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  1. Laboratory of Experimental Hemato-Oncology, CRP-Santé, Luxembourg

    J Paggetti, G Berchem & E Moussay

  2. Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg

    G Berchem

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  1. J Paggetti
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  2. G Berchem
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Correspondence to E Moussay.

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JP and EM designed and performed the research, analyzed the data and wrote the manuscript; GB recruited CLL patients and edited the manuscript.

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Paggetti, J., Berchem, G. & Moussay, E. Stromal cell-induced miRNA alteration in chronic lymphocytic leukemia: how a minute and unavoidable cell contamination impairs miRNA profiling. Leukemia 27, 1773–1776 (2013). https://doi.org/10.1038/leu.2013.43

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