Best Practice & Research Clinical Haematology
Volume 20, Issue 3 , Pages 399-413 , September 2007

Cell proliferation and death: Forgotten features of chronic lymphocytic leukemia B cells

  • Nicholas Chiorazzi, MD (Investigator, The Feinstein Institute for Medical Research, and Professor of Medicine and of Cell Biology, Albert Einstein College of Medicine)

      Affiliations

    • Corresponding Author InformationTel.: +1 516 562 1085; Fax: +1 516 562 1011.

References 

  1. Dameshek W. Chronic lymphocytic leukemia – an accumulative disease of immunologically incompetent lymphocytes. Blood. 1967;29(4supplement):566–584
  2. Rai KR, Patel DV. Chronic lymphocytic leukemia. In:  Hoffman R,  Benz E,  Shattil S, et al. editor. Hematology: basic principles and practice. 2nd ed.. New York: Churchill Livingstone; 1995;p. 1308–1321
  3. Pileri SA, Ascani S, Sabattini E, et al. The pathologist's view point. Part I–indolent lymphomas. Haematologica. 2000;85(12):1291–1307
  4. Andreef M. Flow cytometry in leukemia. In:  Melamed MR,  Mendelsohn ML editor. Flow cytometry and cell sorting. New York: Alan R. Liss; 1990;p. 697
  5. Matutes E, Polliack A. Morphological and immunophenotypic features of chronic lymphocytic leukemia. Reviews in Clinical and Experimental Hematology. 2000;4(1):22–47
  6. Ma Y, Mansour A, Bekele BN, et al. The clinical significance of large cells in bone marrow in patients with chronic lymphocytic leukemia. Cancer. 2004;100(10):2167–2175
  7. Lampert IA, Wotherspoon A, Van Noorden S, Hasserjian RP. High expression of CD23 in the proliferation centers of chronic lymphocytic leukemia in lymph nodes and spleen. Human Pathology. 1999;30(6):648–654
  8. Granziero L, Ghia P, Circosta P, et al. Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia. Blood. 2001;97(9):2777–2783
  9. Schmid C, Isaacson PG. Proliferation centres in B-cell malignant lymphoma, lymphocytic (CLL): an immunophenotypic study. Histopathology. 1994;24(5):445–451
  10. Caligaris-Cappio F. Role of the microenvironment in chronic lymphocytic leukaemia. British journal of haematology. 2003;123(3):380–388
  11. Pizzolo G, Chilosi M, Ambrosetti A, et al. Immunohistologic study of bone marrow involvement in B-chronic lymphocytic leukemia. Blood. 1983;62(6):1289–1296
  12. Fluckiger AC, Rossi JF, Bussel A, et al. Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors. Blood. 1992;80(12):3173–3181
  13. Buske C, Gogowski G, Schreiber K, et al. Stimulation of B-chronic lymphocytic leukemia cells by murine fibroblasts, IL-4, anti-CD40 antibodies, and the soluble CD40 ligand. Experimental Hematology. 1997;25(4):329–337
  14. Ghia P, Strola G, Granziero L, et al. Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+, CD40L+ T cells by producing CCL22. European journal of immunology. 2002;32(5):1403–1413
  15. Damle RN, Ghiotto F, Valetto A, et al. B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. Blood. 2002;99(11):4087–4093
  16. Rosenwald A, Alizadeh AA, Widhopf G, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. The Journal of Experimental Medicine. 2001;194(11):1639–1647
  17. Klein U, Tu Y, Stolovitzky GA, et al. Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. The Journal of Experimental Medicine. 2001;194(11):1625–1638
  18. Damle RN, Batliwalla FM, Ghiotto F, et al. Telomere length and telomerase activity delineate distinctive replicative features of the CLL subgroups defined by immunoglobulin V gene mutations. Blood. 2004;103(2):375–382
  19. Zupo S, Isnardi L, Megna M, et al. CD38 expression distinguishes two groups of B-cell chronic lymphocytic leukemias with different responses to anti-IgM antibodies and propensity to apoptosis. Blood. 1996;88(4):1365–1374
  20. Lagneaux L, Delforge A, Bron D, et al. Chronic lymphocytic leukemic B cells but not normal B cells are rescued from apoptosis by contact with normal bone marrow stromal cells. Blood. 1998;91(7):2387–2396
  21. Panayiotidis P, Jones D, Ganeshaguru K, et al. Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro. British Journal of Haematology. 1996;92(1):97–103
  22. Burger JA, Tsukada N, Burger M, et al. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000;96(8):2655–2663
  23. Bernal A, Pastore RD, Asgary Z, et al. Survival of leukemic B cells promoted by engagement of the antigen receptor. Blood. 2001;98(10):3050–3057
  24. Zupo S, Massara R, Dono M, et al. Apoptosis or plasma cell differentiation of CD38-positive B-chronic lymphocytic leukemia cells induced by cross-linking of surface IgM or IgD. Blood. 2000;95(4):1199–1206
  25. Ranheim EA, Kipps TJ. Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal. The Journal of Experimental Medicine. 1993;177(4):925–935
  26. Deaglio S, Vaisitti T, Bergui L, et al. CD38 and CD100 lead a network of surface receptors relaying positive signals for CLL growth and survival. Blood. 2005;105:3042–3050
  27. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nature Immunology. 2004;5(10):987–995
  28. Orsini E, Foa R. Cytokines and regulatory molecules in the pathogenesis and clinical course of B-cell chronic lymphocytic leukemia. 2nd ed.. New York: Marcel Dekker, Inc; 2001;
  29. Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood. 2006;107(5):1761–1767
  30. Flad GD, Huber C, Bremer K, et al. Impaired recirculation of B lymphocytes in chronic lymphocytic leukemia. European Journal of Immunology. 1973;3(11):688–693
  31. Stryckmans PA, Debusscher L, Collard E. Cell kinetics in chronic lymphocytic leukaemia (CLL). Clinical Haematology. 1977;6(1):159–167
  32. Hultdin M, Rosenquist R, Thunberg U, et al. Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications. British Journal of Cancer. 2003;88(4):593–598
  33. Waldman FM, Chew K, Ljung BM, et al. A comparison between bromodeoxyuridine and 3H thymidine labeling in human breast tumors. Modern Pathology. 1991;4(6):718–722
  34. Gratzner HG. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science. 1982;218(4571):474–475
  35. Asher E, Payne CM, Bernstein C. Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis, light microscopy and electron microscopy. II. Induction of non-classic apoptosis (‘para-apoptosis’) by tritiated thymidine. Leukemia & Lymphoma. 1995;19(1-2):107–119
  36. Rocha B, Penit C, Baron C, et al. Accumulation of bromodeoxyuridine-labeled cells in central and peripheral lymphoid organs: minimal estimates of production and turnover rates of mature lymphocytes. European Journal of Immunology. 1990;20(8):1697–1708
  37. Reichard P. Interactions between deoxyribonucleotide and DNA synthesis. Annual Review of Biochemistry. 1988;57:349–374
  38. Cohen A, Barankiewicz J, Lederman HM, Gelfand EW. Purine and pyrimidine metabolism in human T lymphocytes. Regulation of deoxyribonucleotide metabolism. The Journal of Biological Chemistry. 1983;258(20):12334–12340
  39. Hellerstein MK. Measurement of T-cell kinetics: recent methodologic advances. Immunology Today. 1999;20(10):438–441
  40. Neese RA, Misell LM, Turner S, et al. Measurement in vivo of proliferation rates of slow turnover cells by 2H2O labeling of the deoxyribose moiety of DNA. Proceedings of the National Academy of Sciences of the USA. 2002;99(24):15345–15350
  41. Neese RA, Siler SQ, Cesar D, et al. Advances in the stable isotope-mass spectrometric measurement of DNA synthesis and cell proliferation. Analytical Biochemistry. 2001;298(2):189–195
  42. Hellerstein M, Hanley MB, Cesar D, et al. Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. Nature Medicine. 1999;5(1):83–89[see comments]
  43. McCune JM, Hanley MB, Cesar D, et al. Factors influencing T-cell turnover in HIV-1-seropositive patients. The Journal of Clinical Investigation. 2000;105(5):R1–R8
  44. Mohri H, Perelson AS, Tung K, et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. The Journal of Experimental Medicine. 2001;194(9):1277–1287
  45. Messmer BT, Messmer D, Allen SL, et al. In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. The Journal of Clinical Investigation. 2005;115(3):755–764
  46. Zimmerman TS, Godwin HA, Perry S. Studies of leukocyte kinetics in chronic lymphocytic leukemia. Blood. 1968;31(3):277–291
  47. Schiffer LM, Chanana AD, Cronkite EP, et al. Lymphocyte kinetics in chronic lymphocytic leukaemia (CLL) studied by ECIB. British Journal of Haematology. 1969;17(4):408
  48. Theml H, Trepel G, Schick P, et al. Kinetics of lymphocytes in chronic lymphocytic leukemia: studies using continuous 3H-thymidine infusion in two patients. Blood. 1973;42:623
  49. Theml H, Love R, Begemann H. Factors in the pathomechanism of chronic lymphocytic leukemia. Annual Review of Medicine. 1977;28:131–141
  50. Cheson BD, Bennet JM, Grever M, et al. National Cancer Institute-sponsored working group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87(12):4990–4997
  51. Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94(6):1840–1847
  52. Deaglio S, Vaisitti T, Aydin S, et al. In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia. Blood. 2006;15;108(4):1135–1144
  53. Calissano C, Damle R, Banapour T, et al. In vivo labeling of newly synthesized DNA suggests that the CD38+ fraction is enriched in proliferating cells within a clone of chronic lymphocytic leukemia B cells. Blood. 2006;108(11):12a–13a
  54. Damle R, Allen S, Rai KR, Chiorazzi N. CD38 expression identifies an active subset of proliferating cells within the clonal population in chronic lymphocytic leukemia patients (in vitro analysis). Blood. 2006;108(11):13a
  55. Zupo S, Cutrona G, Mangiola M, Ferrarini M. Role of surface IgM and IgD on survival of the cells from B-cell chronic lymphocytic leukemia. Blood. 2002;99(6):2277–2278
  56. Lanham S, Hamblin T, Oscier D, et al. Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia. Blood. 2003;101(3):1087–1093
  57. Pepper C, Ward R, Lin TT, et al. Highly purified CD38(+) and CD38(−) sub-clones derived from the same chronic lymphocytic leukemia patient have distinct gene expression signatures despite their monoclonal origin. Leukemia. 2007;21(4):687–696
  58. Lam KP, Kuhn R, Rajewsky K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell. 1997;90(6):1073–1083
  59. Woodland RT, Schmidt MR. Homeostatic proliferation of B cells. Seminars in Immunology. 2005;17(3):209–217
  60. Cancro MP. The BLyS family of ligands and receptors: an archetype for niche-specific homeostatic regulation. Immunological Reviews. 2004;202:237–249
  61. Chiorazzi N, Ferrarini M. B Cell Chronic Lymphocytic Leukemia: Lessons learned from studies of the B cell antigen receptor. Annual Review of Immunology. 2003;21:841–894
  62. Stevenson FK, Caligaris-Cappio F. Chronic lymphocytic leukemia: revelations from the B-cell receptor. Blood. 2004;103(12):4389–4395
  63. Chiorazzi N, Rai KR, Ferrarini M. Chronic Lymphocytic Leukemia. The New England Journal of Medicine. 2005;352(8):804–815
  64. Schroeder HW, Dighiero G. The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody repertoire. Immunology Today. 1994;15(6):288–294
  65. Fais F, Ghiotto F, Hashimoto S, et al. Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. The Journal of Clinical Investigation. 1998;102(8):1515–1525
  66. Tobin G, Thunberg U, Johnson A, et al. Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted V{lambda}2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope. Blood. 2003;101(12):4952–4957
  67. Ghiotto F, Fais F, Valetto A, et al. Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia. The Journal of Clinical Investigation. 2004;113(7):1008–1016
  68. Messmer BT, Albesiano E, Efremov DG, et al. Multiple distinct sets of stereotyped antigen receptors indicate a key role for antigen in promoting chronic lymphocytic leukemia. The Journal of Experimental Medicine. 2004;200:519–525
  69. Tobin G, Thunberg U, Karlsson K, et al. Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia. Blood. 2004;104(9):2879–2885
  70. Widhopf GF, Rassenti LZ, Toy TL, et al. Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins. Blood. 2004;104(8):2499–2504
  71. Stamatopoulos K, Belessi C, Moreno C, et al. Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations. Blood. 2007;109(1):259–270
  72. Sthoeger ZM, Wakai M, Tse DB, et al. Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia. The Journal of Experimental Medicine. 1989;169(1):255–268
  73. Borche L, Lim A, Binet JL, Dighiero G. Evidence that chronic lymphocytic leukemia B lymphocytes are frequently committed to production of natural autoantibodies. Blood. 1990;76(3):562–569
  74. Herve M, Xu K, Ng Y-S, et al. Unmutated and mutated chronic lymphocytic leukemia derive from common self-reactive B cell precursors despite expressing different antibody reactivity. The Journal of Clinical Investigation. 2005;115:1636–1643
  75. Chu CC, Wang XB, Hatzi K, et al. CLL antibodies comprised of stereotypic VH1-69, D3-16, and JH3 rearrangements immunoprecipitate cellular protein(s). Blood. 2006;108(11):797a
  76. Catera R, Hatzi K, Chu CC, et al. Polyreactive monoclonal antibodies synthesized by some CLL cells recognize specific antigens on viable and apoptotic T cells. Blood. 2006;108(11):796a
  77. Hatzi K, Catera R, Ferrarini M, et al. B-cell chronic lymphocytic leukemia (CLL) cells expresss antibodies reactive with antigenic epitopes expressed on the surface of common bacteria. Blood. 2006;108(11):12a
  78. Niiro H, Clark EA. Regulation of B-cell fate by antigen-receptor signals. Nature Reviews. Immunology. 2002;2(12):945–956
  79. Petlickovski A, Laurenti L, Li X, et al. Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells. Blood. 2005;105(12):4820–4827
  80. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. The New England Journal of Medicine. 2000;343(26):1910–1916
  81. Krober A, Seiler T, Benner A, et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood. 2002;100(4):1410–1416
  82. Ottaggio L, Viaggi S, Zunino A, et al. Chromosome aberrations evaluated by comparative genomic hybridization in B-cell chronic lymphocytic leukemia: correlation with CD38 expression. Haematologica. 2003;88(7):769–777
  83. Lin K, Sherrington PD, Dennis M, et al. Relationship between p53 dysfunction, CD38 expression, and IgV(H) mutation in chronic lymphocytic leukemia. Blood. 2002;100(4):1404–1409

PII: S1521-6926(07)00044-8

doi: 10.1016/j.beha.2007.03.007

Best Practice & Research Clinical Haematology
Volume 20, Issue 3 , Pages 399-413 , September 2007

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