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CD49d expression identifies a chronic-lymphocytic leukemia subset with high levels of mobilized circulating CD34+ hemopoietic progenitors cells

Leukemia volume 28, pages 705–708 (2014)Cite this article

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CD49d is a strong negative prognosticator in chronic lymphocytic leukemia (CLL), marking a subset of ∼40% of CLL patients characterized by aggressive and accelerated clinical course.1, 2 Functionally, CD49d, the α4 integrin subunit, has a key role in CLL microenvironmental interactions by binding to fibronectin (FN) and vascular-cell adhesion molecule-1 (VCAM-1).3, 4 CD49d is known to be associated with another CLL-negative prognosticator, CD38, which acts both as a receptor for the endothelial cell marker CD31 and as an enhancer of CD49d-mediated adhesion to FN and VCAM-1 substrates.1, 2, 5, 6 The role of CD49d as a key adhesion molecule involved in disease pathogenesis has also been described in auto-immune diseases, such as multiple sclerosis (MS) where CD49d is responsible for migration of leukocytes through the blood–brain barrier to sites of inflammation. The use of the humanized anti-CD49d monoclonal antibody, natalizumab, has been successfully employed in MS clinical trials to prevent CD49d-mediated leukocyte transmigration.7 Notably, an increased number of circulating CD34+ hemopoietic progenitor cells (HPC) has been documented upon natalizumab treatment of MS patients, in keeping with the notion of high CD49d expression by HPC, and of the relevance of CD49d-mediated microenvironmental interactions to maintain HPC in the context of the hemopoietic niche.8, 9

Here, we focused on the amount of circulating HPC in peripheral blood (PB) samples of CLL cases with different CD49d expression levels.

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Acknowledgements

This work was supported in part by: Ministero della Salute, Ricerca Finalizzata IRCCS, Progetto Giovani Ricercatori no GR-2010-2317594, no GR-2009-1475467 and no GR-2008-1138053, Rome, Italy; Fondazione Internazionale di Ricerca in Medicina Sperimentale; Associazione Italiana contro le Leucemie, linfomi e mielomi, Venezia Section, Pramaggiore Group, Italy; Ricerca Scientifica Applicata, Regione Friuli Venezia Giulia (‘Linfonet’ Project), Trieste, Italy; the Associazione Italiana Ricerca Cancro, Special Program Molecular Clinical Oncology, 5 × 1000, no 10007; Investigator Grant IG-13227, and MFAG-10327, Milan, Italy; ‘5 × 1000 Intramural Program’, Centro di Riferimento Oncologico, Aviano, Italy.

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Authors and Affiliations

  1. Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy

    F M Rossi, A Zucchetto, E Tissino, M Dal Bo, R Bomben, C Caldana, F Pozzo & V Gattei

  2. Division of Hematology, S.Eugenio Hospital and University of Tor Vergata, Rome, Italy

    G Del Poeta

  3. Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

    D Rossi & G Gaidano

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  1. F M Rossi
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Correspondence to F M Rossi.

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Rossi, F., Zucchetto, A., Tissino, E. et al. CD49d expression identifies a chronic-lymphocytic leukemia subset with high levels of mobilized circulating CD34+ hemopoietic progenitors cells. Leukemia 28, 705–708 (2014). https://doi.org/10.1038/leu.2013.331

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