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Non-malignant B cells and chronic lymphocytic leukemia cells induce a pro-survival phenotype in CD14+ cells from peripheral blood

Leukemia volume 25, pages 722–726 (2011)Cite this article

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Chronic lymphocytic leukemia (CLL) is a malignant disease characterized by the accumulation of mature CD5+ B cells in the blood, bone marrow and secondary lymphoid organs.1 Unlike most tumor entities, there is only a small proportion of CLL cells that proliferate.2 This has led to the hypothesis that the accumulation of CLL cells in vivo is not due to increased proliferation rates, but rather due to resistance to apoptosis.1 In CLL, resistance to apoptosis is supported by microenvironmental signals, as CLL cells cultured without support in vitro rapidly undergo apoptosis. In vitro, apoptosis of CLL cells can be prevented by co-culture with supporting cells, either indirectly through soluble factors and/or by direct interaction through cell-surface receptors.3

From peripheral blood monocytes (PBMCs) of CLL patients, a subset of cells (CD14+ cells) differentiate in vitro into large, round, adherent cells (‘Nurse-like cells’, NLCs) that assist in survival of CLL cells.4 Cells that are morphologically and immunophenotypically similar to NLCs can also be differentiated from CD14+ PBMCs of healthy donors by cultivating them in vitro with CLL cells.5 In vivo, NLCs have been described to be present in the spleen and lymph nodes of CLL patients, suggesting that NLCs might promote survival of CLL cells also in these tissues.5, 6 Several proteins that are involved in the pro-survival capabilities of NLCs have been identified: CXCL12,4 CXCL13,6 BAFF (B-cell activating factor of the tumor necrosis factor family),7 APRIL (a proliferation-inducing ligand)7 and CD31 (PECAM1).8 NLCs have an expression profile of surface and cytoplasmic antigens that is distinct from that of other cells of the myelo-monocytic lineage.5 NLCs have a significantly higher CD68 expression compared with monocytes, macrophages and dendritic cells from healthy donors.5 What remains unclear is whether the differentiation of NLCs is specific to CLL or whether non-malignant B cells can also convert CD14+ PBMCs to cells with pro-survival capacities.

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References

  1. Chiorazzi N, Rai KR, Ferrarini M . Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804–815.

    Article  CAS  Google Scholar 

  2. Messmer BT, Messmer D, Allen SL, Kolitz JE, Kudalkar P, Cesar D et al. In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest 2005; 115: 755–764.

    Article  CAS  Google Scholar 

  3. Burger JA, Ghia P, Rosenwald A, Caligaris-Cappio F . The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood 2009; 114: 3367–3375.

    Article  CAS  Google Scholar 

  4. Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell’Aquila M, Kipps TJ . Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood 2000; 96: 2655–2663.

    CAS  Google Scholar 

  5. Tsukada N, Burger JA, Zvaifler NJ, Kipps TJ . Distinctive features of ‘nurselike’ cells that differentiate in the context of chronic lymphocytic leukemia. Blood 2002; 99: 1030–1037.

    Article  CAS  Google Scholar 

  6. Bürkle A, Niedermeier M, Schmitt-Gräff A, Wierda WG, Keating MJ, Burger JA . Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B-cell chronic lymphocytic leukemia. Blood 2007; 110: 3316–3325.

    Article  Google Scholar 

  7. Nishio M, Endo T, Tsukada N, Ohata J, Kitada S, Reed JC et al. Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1alpha. Blood 2005; 106: 1012–1020.

    Article  CAS  Google Scholar 

  8. Deaglio S, Vaisitti T, Bergui L, Bonello L, Horenstein AL, Tamagnone L et al. CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival. Blood 2005; 105: 3042–3050.

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to acknowledge Martina Seiffert, Danilo Allegra, Angela Philippen, Bettina Klohs, Lars Bullinger, Stefan Fröhling and Claudia Scholl for helpful discussions and Frederic Blond for the bioinformatics support. We would also like to acknowledge the excellent collaboration with Bernd Korn from the German Cancer Research Center core facility Genome and Proteome. This work was supported by funding from DJCLS SP 08/05, DJCLS R 06/13, the Helmholtz Alliance for Systems Biology and the Max-Eder-Nachwuchsgruppenprogramm of the Deutsche Krebshilfe (No. 107239).

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  1. Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany

    N Bhattacharya, S Diener, I S Idler, J Rauen, A Habermann, T Zenz, H Döhner, S Stilgenbauer & D Mertens

  2. Institute of Pathology, University of Ulm, Ulm, Germany

    T F Barth & P Möller

  3. Cooperation Unit ‘Mechanisms of Leukemogenesis’, German Cancer Research Center (DKFZ), Heidelberg, Germany

    D Mertens

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  1. N Bhattacharya
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Correspondence to D Mertens.

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Bhattacharya, N., Diener, S., Idler, I. et al. Non-malignant B cells and chronic lymphocytic leukemia cells induce a pro-survival phenotype in CD14+ cells from peripheral blood. Leukemia 25, 722–726 (2011). https://doi.org/10.1038/leu.2010.306

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