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Chronic lymphocytic leukemia

Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels

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References

  1. 1.

    Cartron G, Watier H, Golay J, Solal-Celigny P. From the bench to the bedside: ways to improve rituximab efficacy. Blood. 2004;104:2635–42.

    Article  PubMed  CAS  Google Scholar 

  2. 2.

    Bubien JK, Zhou LJ, Bell PD, Frizzell RA, Tedder TF. Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+conductance found constitutively in B lymphocytes. J Cell Biol. 1993;121:1121–32.

    Article  PubMed  CAS  Google Scholar 

  3. 3.

    Morsy DED, Sanyal R, Zaiss AK, Deo R, Muruve DA, Deans JP. Reduced T-dependent humoral immunity in CD20-deficient mice. J Immunol. 2013;191:3112–18.

    Article  PubMed  CAS  Google Scholar 

  4. 4.

    Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IAM, Dolman KM, et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest. 2010;120:214–22.

    Article  PubMed  CAS  Google Scholar 

  5. 5.

    Pavlasova G, Borsky M, Seda V, Cerna K, Osickova J, Doubek M, et al. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. Blood. 2016;128:1609–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. 6.

    Calissano C, Damle RN, Marsilio S, Yan X, Yancopoulos S, Hayes G, et al. Intraclonal complexity in chronic lymphocytic leukemia: fractions enriched in recently born/divided and older/quiescent cells. Mol Med. 2011;17:74–1382.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. 7.

    Golay J, Lazzari M, Facchinetti V, Bernasconi S, Borleri G, Barbui T, et al. CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59. Blood. 2001;98:3383–89.

    Article  PubMed  CAS  Google Scholar 

  8. 8.

    van Meerten T, van Rijn RS, Hol S, Hagenbeek A, Ebeling SB. Complement-induced cell death by rituximab depends on CD20 expression level and acts complementary to antibody-dependent cellular cytotoxicity. Clin Cancer Res. 2006;12:4027–35.

    Article  PubMed  Google Scholar 

  9. 9.

    Zent CS, Elliott MR. Maxed out macs: physiologic cell clearance as a function of macrophage phagocytic capacity. FEBS J. 2017;284:1021–39.

    Article  PubMed  CAS  Google Scholar 

  10. 10.

    Buchner M, Brantner P, Stickel N, Prinz G, Burger M, Bär C, et al. The microenvironment differentially impairs passive and active immunotherapy in chronic lymphocytic leukaemia – CXCR4 antagonists as potential adjuvants for monoclonal antibodies. Br J Haematol. 2010;151:167–78.

    Article  PubMed  CAS  Google Scholar 

  11. 11.

    Mraz M, Zent CS, Church AK, Jelinek DF, Wu X, Pospisilova S, et al. Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin α-4-β-1 (VLA-4) with natalizumab can overcome this resistance. Br J Haematol. 2011;155:53–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. 12.

    Uchida J, Lee Y, Hasegawa M, Liang Y, Bradney A, Oliver JA, et al. Mouse CD20 expression and function. Int Immunol. 2004;16:119–29.

    Article  PubMed  CAS  Google Scholar 

  13. 13.

    D’Avola A, Drennan S, Tracy I, Henderson I, Chiecchio L, Larrayoz M, et al. Surface IgM expression and function are associated with clinical behavior, genetic abnormalities, and DNA methylation in CLL. Blood. 2016;128:816–26.

    Article  PubMed  CAS  Google Scholar 

  14. 14.

    Chen S-S, Chang BY, Chang S, Tong T, Ham S, Sherry B, et al. BTK inhibition results in impaired CXCR4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia. Leukemia. 2016;30:833–43.

    Article  PubMed  CAS  Google Scholar 

  15. 15.

    Kheirallah S, Caron P, Gross E, Quillet-Mary A, Bertrand-Michel J, Fournié J-J, et al. Rituximab inhibits B-cell receptor signaling. Blood. 2010;115:985–94.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by Ministry of Health of the Czech Republic, grant nr. 16–29622A. All rights reserved. We would like to thank Thomas J. Kipps and Laura Z. Rassenti (UCSD) for inspiring discussion and comments to the study.

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Correspondence to Marek Mraz.

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Pavlasova, G., Borsky, M., Svobodova, V. et al. Rituximab primarily targets an intra-clonal BCR signaling proficient CLL subpopulation characterized by high CD20 levels. Leukemia 32, 2028–2031 (2018). https://doi.org/10.1038/s41375-018-0211-0

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