B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes

Damle RN, Ghiotto F, Valetto A, Albasiano E, Fais F, Yan XJ, Sison CP, Allen SL, Kolitz J, Schulman P, Vinciguerra VP, et al. (2002)
BLOOD 99(11): 4087-4093.

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B-cell chronic lymphocytic leukemia (B-CLL) is considered an accumulative disease of antigen-naive CD5(+) B lymphocytes that circulate in the resting state. However, to evaluate the possibility that B-CLL cells resemble antigen-experienced and activated B cells, we analyzed the expression of markers of cellular activation and differentiation on CD5(+)CD19(+) cells from B-CLL patients and from age-matched healthy donors. The leukemic cells from all B-CLL patients, including those that lack significant numbers of V gene mutations, bear the phenotype of activated B cells based on the overexpression of the activation markers CD23, CD25, CD69, and CD71 and the underexpression of CD22, Fcgamma receptor IIb, CD79b, and immunoglobulin D that are down-regulated by cell triggering and activation. Furthermore, these leukemic cells resemble antigen-experienced lymphocytes in the underexpression of molecules that are down-regulated by cell triggering and in the uniform expression of CD27, an identifier of memory B cells. A comparison of the phenotypes of B-CLL patients with and without immunoglobulin V gene mutations suggests that the 2 subgroups differ both in specific marker expression (CD69, CD71, CD62 L, CD40, CD39, and HLA-DR) and in the time since antigenic stimulation, based on the reciprocal relationship of CD69 and CD71 expression. These findings imply that the leukemic cells from all B-CLL cases (irrespective of V gene mutations) exhibit features of activated and of antigen-experienced B lymphocytes and that the B-CLL cells that differ in immunoglobulin V genotype may have different antigen-encounter histories. (C) 2002 by The American Society of Hematology.
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BLOOD
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99
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4087-4093
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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.
Damle, R. N., Ghiotto, F., Valetto, A., Albasiano, E., Fais, F., Yan, X. J., Sison, C. P., et al. (2002). B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD, 99(11), 4087-4093. doi:10.1182/blood.V99.11.4087
Damle, R. N., Ghiotto, F., Valetto, A., Albasiano, E., Fais, F., Yan, X. J., Sison, C. P., Allen, S. L., Kolitz, J., Schulman, P., et al. (2002). B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD 99, 4087-4093.
Damle, R.N., et al., 2002. B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD, 99(11), p 4087-4093.
R.N. Damle, et al., “B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes”, BLOOD, vol. 99, 2002, pp. 4087-4093.
Damle, R.N., Ghiotto, F., Valetto, A., Albasiano, E., Fais, F., Yan, X.J., Sison, C.P., Allen, S.L., Kolitz, J., Schulman, P., Vinciguerra, V.P., Budde, P., Frey, J., Rai, K.R., Ferrarini, M., Chiorazzi, N.: B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD. 99, 4087-4093 (2002).
Damle, RN, Ghiotto, F, Valetto, A, Albasiano, E, Fais, F, Yan, XJ, Sison, CP, Allen, SL, Kolitz, J, Schulman, P, Vinciguerra, VP, Budde, P, Frey, Jürgen, Rai, KR, Ferrarini, M, and Chiorazzi, N. “B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes”. BLOOD 99.11 (2002): 4087-4093.

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Comparison of Bcl-2, CD38 and ZAP-70 Expression in Chronic Lymphocytic Leukemia.
Sargent RL, Craig FE, Swerdlow SH., Int J Clin Exp Pathol 2(6), 2009
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Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells.
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Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression.
Ding W, Nowakowski GS, Knox TR, Boysen JC, Maas ML, Schwager SM, Wu W, Wellik LE, Dietz AB, Ghosh AK, Secreto CR, Medina KL, Shanafelt TD, Zent CS, Call TG, Kay NE., Br J Haematol 147(4), 2009
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Nonstochastic pairing of immunoglobulin heavy and light chains expressed by chronic lymphocytic leukemia B cells is predicated on the heavy chain CDR3.
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Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis.
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Aurran-Schleinitz T, Arnoulet C, Ivanov V, Coso D, Rey J, Schiano JM, Stoppa AM, Bouabdallah R, Gastaut JA., Rev Med Interne 29(5), 2008
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Analysis of CD23 antigen expression in B-chronic lymphocytic leukaemia and its correlation with clinical parameters.
Jurisic V, Colovic N, Kraguljac N, Atkinson HD, Colovic M., Med Oncol 25(3), 2008
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A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies.
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FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia.
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Combined automated cell and flow cytometric analysis enables recognition of persistent polyclonal B-cell lymphocytosis (PPBL), a study of 25 patients.
Schmidt-Hieber M, Burmeister T, Weimann A, Nagorsen D, Hofmann WK, Thiel E, Schwartz S., Ann Hematol 87(10), 2008
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Predominantly post-transcriptional regulation of activation molecules in chronic lymphocytic leukemia: the case of transferrin receptors.
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Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA.
Chu CC, Catera R, Hatzi K, Yan XJ, Zhang L, Wang XB, Fales HM, Allen SL, Kolitz JE, Rai KR, Chiorazzi N., Blood 112(13), 2008
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Chronic lymphocytic leukemia cells recognize conserved epitopes associated with apoptosis and oxidation.
Catera R, Silverman GJ, Hatzi K, Seiler T, Didier S, Zhang L, Hervé M, Meffre E, Oscier DG, Vlassara H, Scofield RH, Chen Y, Allen SL, Kolitz J, Rai KR, Chu CC, Chiorazzi N., Mol Med 14(11-12), 2008
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Microenvironmental influences in chronic lymphocytic leukaemia: the role of antigen stimulation.
Ghia P, Chiorazzi N, Stamatopoulos K., J Intern Med 264(6), 2008
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Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification.
Volkheimer AD, Weinberg JB, Beasley BE, Whitesides JF, Gockerman JP, Moore JO, Kelsoe G, Goodman BK, Levesque MC., Blood 109(4), 2007
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Fc receptor-like molecules.
Davis RS., Annu Rev Immunol 25(), 2007
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From normal to clonal B cells: Chronic lymphocytic leukemia (CLL) at the crossroad between neoplasia and autoimmunity.
Ghia P, Scielzo C, Frenquelli M, Muzio M, Caligaris-Cappio F., Autoimmun Rev 7(2), 2007
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CD5 links humoral autoimmunity with B-cell chronic lymphocytic leukemia.
Mankai A, Bordron A, Renaudineau Y, Berthou C, Ghedira I, Youinou P., Expert Rev Clin Immunol 3(3), 2007
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CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia.
Pulte D, Olson KE, Broekman MJ, Islam N, Ballard HS, Furman RR, Olson AE, Marcus AJ., J Transl Med 5(), 2007
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CD23 is recognized as tumor-associated antigen (TAA) in B-CLL by CD8+ autologous T lymphocytes.
Bund D, Mayr C, Kofler DM, Hallek M, Wendtner CM., Exp Hematol 35(6), 2007
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CD39/NTPDase-1 activity and expression in normal leukocytes.
Pulte ED, Broekman MJ, Olson KE, Drosopoulos JH, Kizer JR, Islam N, Marcus AJ., Thromb Res 121(3), 2007
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CD5+ B cells with the features of subepithelial B cells found in human tonsils.
Dono M, Burgio VL, Colombo M, Sciacchitano S, Reverberi D, Tarantino V, Cutrona G, Chiorazzi N, Ferrarini M., Eur J Immunol 37(8), 2007
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CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells.
Damle RN, Temburni S, Calissano C, Yancopoulos S, Banapour T, Sison C, Allen SL, Rai KR, Chiorazzi N., Blood 110(9), 2007
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Expression of inhibitory receptor ILT3 on neoplastic B cells is associated with lymphoid tissue involvement in chronic lymphocytic leukemia.
Colovai AI, Tsao L, Wang S, Lin H, Wang C, Seki T, Fisher JG, Menes M, Bhagat G, Alobeid B, Suciu-Foca N., Cytometry B Clin Cytom 72(5), 2007
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The normal counterpart to the chronic lymphocytic leukemia B cell.
Caligaris-Cappio F, Ghia P., Best Pract Res Clin Haematol 20(3), 2007
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Peripheral circulating activated b-cell populations are associated with nephritis and disease activity in patients with systemic lupus erythematosus.
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Transferrin receptor-1 and 2 expression in chronic lymphocytic leukemia.
Smilevska T, Stamatopoulos K, Samara M, Belessi C, Tsompanakou A, Paterakis G, Stavroyianni N, Athanasiadou I, Chiotoglou I, Hadzidimitriou A, Athanasiadou A, Douka V, Saloum R, Laoutaris N, Anagnostopoulos A, Fassas A, Stathakis N, Kollia P., Leuk Res 30(2), 2006
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Constitutive and activation-inducible cyclooxygenase-2 expression enhances survival of chronic lymphocytic leukemia B cells.
Ryan EP, Pollock SJ, Kaur K, Felgar RE, Bernstein SH, Chiorazzi N, Phipps RP., Clin Immunol 120(1), 2006
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B lymphocytes in humans express ZAP-70 when activated in vivo.
Cutrona G, Colombo M, Matis S, Reverberi D, Dono M, Tarantino V, Chiorazzi N, Ferrarini M., Eur J Immunol 36(3), 2006
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High Mda-7 expression promotes malignant cell survival and p38 MAP kinase activation in chronic lymphocytic leukemia.
Sainz-Perez A, Gary-Gouy H, Portier A, Davi F, Merle-Beral H, Galanaud P, Dalloul A., Leukemia 20(3), 2006
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Emerging drugs for chronic lymphocytic leukaemia.
Yee KW, O'Brien SM., Expert Opin Emerg Drugs 11(1), 2006
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ZAP-70 is expressed by normal and malignant human B-cell subsets of different maturational stage.
Scielzo C, Camporeale A, Geuna M, Alessio M, Poggi A, Zocchi MR, Chilosi M, Caligaris-Cappio F, Ghia P., Leukemia 20(4), 2006
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Similarities and differences between the light and heavy chain Ig variable region gene repertoires in chronic lymphocytic leukemia.
Ghiotto F, Fais F, Albesiano E, Sison C, Valetto A, Gaidano G, Reinhardt J, Kolitz JE, Rai K, Allen SL, Ferrarini M, Chiorazzi N., Mol Med 12(11-12), 2006
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The CD38 ectoenzyme family: advances in basic science and clinical practice.
Morabito F, Damle RN, Deaglio S, Keating M, Ferrarini M, Chiorazzi N., Mol Med 12(11-12), 2006
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Differential control of G0 programme in chronic lymphocytic leukaemia: a novel prognostic factor.
Danilov AV, Klein AK, Lee HJ, Baez DV, Huber BT., Br J Haematol 128(4), 2005
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Chronic lymphocytic leukemia.
Chiorazzi N, Rai KR, Ferrarini M., N Engl J Med 352(8), 2005
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Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation.
Mackus WJ, Kater AP, Grummels A, Evers LM, Hooijbrink B, Kramer MH, Castro JE, Kipps TJ, van Lier RA, van Oers MH, Eldering E., Leukemia 19(3), 2005
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Mechanisms of B-cell lymphoma pathogenesis.
Küppers R., Nat Rev Cancer 5(4), 2005
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Identification of a potential role for POU2AF1 and BTG4 in the deletion of 11q23 in chronic lymphocytic leukemia.
Auer RL, Starczynski J, McElwaine S, Bertoni F, Newland AC, Fegan CD, Cotter FE., Genes Chromosomes Cancer 43(1), 2005
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HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses.
Scielzo C, Ghia P, Conti A, Bachi A, Guida G, Geuna M, Alessio M, Caligaris-Cappio F., J Clin Invest 115(6), 2005
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Signature of B-CLL with different prognosis by Shrunken centroids of surface antigen expression profiling.
Zucchetto A, Sonego P, Degan M, Bomben R, Dal Bo M, Russo S, Attadia V, Rupolo M, Buccisano F, Del Principe MI, Del Poeta G, Pucillo C, Colombatti A, Campanini R, Gattei V., J Cell Physiol 204(1), 2005
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Differential expression of CD 180 and IgM by B-cell chronic lymphocytic leukaemia cells using mutated and unmutated immunoglobulin VH genes.
Porakishvili N, Kulikova N, Jewell AP, Youinou PY, Yong K, Nathwani A, Heelan B, Duke V, Hamblin TJ, Wallace P, Ely P, Clark EA, Lydyard PM., Br J Haematol 131(3), 2005
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ZAP-70 in B cell malignancies.
Orchard J, Ibbotson R, Best G, Parker A, Oscier D., Leuk Lymphoma 46(12), 2005
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CD27 distinguishes two phases in bone marrow infiltration of splenic marginal zone lymphoma.
Franco V, Florena AM, Ascani S, Paulli M, Salvato M, Pileri SA., Histopathology 44(4), 2004
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Analysis of IgV gene mutations in B cell chronic lymphocytic leukaemia according to antigen-driven selection identifies subgroups with different prognosis and usage of the canonical somatic hypermutation machinery.
Degan M, Bomben R, Bo MD, Zucchetto A, Nanni P, Rupolo M, Steffan A, Attadia V, Ballerini PF, Damiani D, Pucillo C, Poeta GD, Colombatti A, Gattei V., Br J Haematol 126(1), 2004
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Histopathology of B-cell chronic lymphocytic leukemia.
Pileri SA, Sabattini E, Agostinelli C, Bodega L, Rossi M, Zinzani PL, Marafioti T., Hematol Oncol Clin North Am 18(4), 2004
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The nature and origin of the B-chronic lymphocytic leukemia cell: a tentative model.
Caligaris-Cappio F, Ghia P., Hematol Oncol Clin North Am 18(4), 2004
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Surface antigen expression and correlation with variable heavy-chain gene mutation status in chronic lymphocytic leukemia.
Vilpo J, Tobin G, Hulkkonen J, Hurme M, Thunberg U, Sundström C, Vilpo L, Rosenquist R., Eur J Haematol 70(1), 2003
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Biological and clinical heterogeneity of B-cell chronic lymphocytic leukemia.
D'Arena G, Di Renzo N, Brugiatelli M, Vigliotti ML, Keating MJ., Leuk Lymphoma 44(2), 2003
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DAB389IL2 (ONTAK) fusion protein therapy of chronic lymphocytic leukaemia.
Frankel AE, Fleming DR, Powell BL, Gartenhaus R., Expert Opin Biol Ther 3(1), 2003
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Early gene activation in chronic leukemic B lymphocytes induced toward a plasma cell phenotype.
Segel GB, Woodlock TJ, Xu J, Li L, Felgar RE, Ryan DH, Lichtman MA, Wang N., Blood Cells Mol Dis 30(3), 2003
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Human peripheral B cells: a different cytometric point of view.
Carbonari M, Tedesco T, Fiorilli M., Cytometry A 53(2), 2003
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Immunobiology of chronic lymphocytic leukemia.
Kipps TJ., Curr Opin Hematol 10(4), 2003
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Towards molecular diagnosis and targeted therapy of lymphoid malignancies.
Wiestner A, Staudt LM., Semin Hematol 40(4), 2003
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Role of the microenvironment in chronic lymphocytic leukaemia.
Caligaris-Cappio F., Br J Haematol 123(3), 2003
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Chronic lymphocytic leukemia B cells can undergo somatic hypermutation and intraclonal immunoglobulin V(H)DJ(H) gene diversification.
Gurrieri C, McGuire P, Zan H, Yan XJ, Cerutti A, Albesiano E, Allen SL, Vinciguerra V, Rai KR, Ferrarini M, Casali P, Chiorazzi N., J Exp Med 196(5), 2002
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Ongoing in vivo immunoglobulin class switch DNA recombination in chronic lymphocytic leukemia B cells.
Cerutti A, Zan H, Kim EC, Shah S, Schattner EJ, Schaffer A, Casali P., J Immunol 169(11), 2002
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Do CLL B cells correspond to naive or memory B-lymphocytes? Evidence for an active Ig switch unrelated to phenotype expression and Ig mutational pattern in B-CLL cells.
Oppezzo P, Magnac C, Bianchi S, Vuillier F, Tiscornia A, Dumas G, Payelle-Brogard B, Ajchenbaum-Cymbalista F, Dighiero G, Pritsch O., Leukemia 16(12), 2002
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