Immunogenetic studies of chronic lymphocytic leukemia: Revelations and speculations about ontogeny and clinical evolution

Cancer Research

Volumn 74, Issue 16, 2014, Pages 4211-4216

  Vardi, Anna ^a,b   Agathangelidis, Andreas ^c   Sutton, Lesley Ann ^d   Ghia, Paolo ^c,e   Rosenquist, Richard ^d   Stamatopoulos, Kostas ^a,b,d  

^a INFORMATION TECHNOLOGIES INSTITUTE   (Greece)

^b G PAPANICOLAOU HOSPITAL   (Greece)

^c SAN RAFFAELE HOSPITAL   (Italy)

^d UPPSALA UNIVERSITY   (Sweden)

^e VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL; CHRONIC LYMPHATIC LEUKEMIA; GENETICS; HUMAN; IMMUNOGENETICS; IMMUNOLOGY; PATHOLOGY;

ANIMALS; HUMANS; IMMUNOGENETICS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL;

EID: 84905980544     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-14-0630     Document Type: Review

References (49)

1. Schroeder HW Jr, Dighiero G. The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody repertoire. Immunol Today 1994;15:288-94. (Pubitemid 24170523)
2. Hashimoto S, Dono M, Wakai M, Allen SL, Lichtman SM, Schulman P, et al. Somatic diversification and selection of immunoglobulin heavy and light chain variable region genes in IgG+ CD5+ chronic lymphocytic leukemia B cells. J Exp Med 1995;181:1507-17.
3. Fais F, Ghiotto F, Hashimoto S, Sellars B, Valetto A, Allen SL, et al. Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest 1998;102:1515-25. (Pubitemid 28492218)
4. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999;94:1848-54 (Pubitemid 29430400)
5. Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999;94:1840-7. (Pubitemid 29430399)
6. Dighiero G. CLL biology and prognosis. Hematology Am Soc Hematol Educ Program 2005;1:278-84.
7. Dighiero G, Hamblin TJ. Chronic lymphocytic leukaemia. Lancet 2008;371:1017-29 (Pubitemid 351389535)
8. Lin K, Manocha S, Harris RJ, Matrai Z, Sherrington PD, Pettitt AR. High frequency of p53 dysfunction and low level of VH mutation in chronic lymphocytic leukemia patients using the VH3-21 gene segment. Blood 2003;102:1145-6. (Pubitemid 36917821)
9. Tobin G, Thunberg U, Johnson A, Thorn I, Soderberg O, Hultdin M, et al. Somatically mutated Ig V(H)3-21 genes characterize anew subset of chronic lymphocytic leukemia. Blood 2002;99:2262-4. (Pubitemid 34525519)
10. Tobin G, Thunberg U, Johnson A, Eriksson I, Soderberg O, Karlsson K, et al. Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted Vlambda2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope. Blood 2003;101:4952-7. (Pubitemid 36857759)
11. Tobin G, Thunberg U, Karlsson K, Murray F, Laurell A, Willander 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;104:2879-85. (Pubitemid 39434975)
12. Ghiotto F, Fais F, Valetto A, Albesiano E, Hashimoto S, Dono M, et al. Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia. J Clin Invest 2004;113:1008-16. (Pubitemid 38544122)
13. Agathangelidis A, Darzentas N, Hadzidimitriou A, Brochet X, Murray F, Yan XJ, et al. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood 2012;119:4467-75.
14. Stamatopoulos K, Belessi C, Moreno C, Boudjograh M, Guida G, Smilevska T, et al. Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations. Blood 2007;109:259-70. (Pubitemid 46070124)
15. Thorselius M, Krober A, Murray F, Thunberg U, Tobin G, Buhler A, et al. Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status. Blood 2006;107:2889-94.
16. Athanasiadou A, Stamatopoulos K, Gaitatzi M, Stavroyianni N, Fassas A, Anagnostopoulos A. Recurrent cytogenetic findings in subsets of patients with chronic lymphocytic leukemia expressing IgG-switched stereotyped immunoglobulins. Haematologica 2008;93:473-4. (Pubitemid 351398656)
17. Strefford JC, Sutton LA, Baliakas P, Agathangelidis A, Malcikova J, Plevova K, et al. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #2. Leukemia 2013;27:2196-9.
18. Rossi D, Spina V, Bomben R, Rasi S, Dal-Bo M, Bruscaggin A, et al. Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia. Blood 2013;121:4902-5.
19. Murray F, Darzentas N, Hadzidimitriou A, Tobin G, Boudjogra M, Scielzo C, et al. Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis. Blood 2008;111:1524-33. (Pubitemid 351213442)
20. Chu CC, Catera R, Zhang L, Didier S, Agagnina BM, Damle RN, et al. Many chronic lymphocytic leukemia antibodies recognize apoptotic cells with exposed nonmuscle myosin heavy chain IIA: implications for patient outcome and cell of origin. Blood 2010;115:3907-15.
21. Palacios F, Moreno P, Morande P, Abreu C, Correa A, Porro V, et al. High expression of AID and active class switch recombination might account for a more aggressive disease in unmutated CLL patients: link with an activated microenvironment in CLL disease. Blood 2010;115:4488-96.
22. Patten PE, Chu CC, Albesiano E,Damle RN, Yan XJ, Kim D, et al. IGHV-unmutated and IGHV-mutated chronic lymphocytic leukemia cells produce activation-induced deaminase protein with a full range of biologic functions. Blood 2012;120:4802-11.
23. Muzio M, Apollonio B, Scielzo C, Frenquelli M, Vandoni I, Boussiotis V, et al. Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature of anergy. Blood 2008;112:188-95.
24. Mockridge CI, Potter KN, Wheatley I, Neville LA, Packham G, Stevenson FK. Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status. Blood 2007;109:4424-31. (Pubitemid 46743412)
25. Lanham S, Hamblin T, Oscier D, Ibbotson R, Stevenson F, Packham G. Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia. Blood 2003;101:1087-93. (Pubitemid 36139383)
26. Coelho V, Krysov S, Ghaemmaghami AM, Emara M, Potter KN, Johnson P, et al. Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins. Proc Natl Acad Sci U S A 2010;107:18587-92.
27. Krysov S, Potter KN, Mockridge CI, Coelho V, Wheatley I, Packham G, et al. Surface IgM of CLL cells displays unusual glycans indicative of engagement of antigen in vivo. Blood 2010;115:4198-205.
28. Herve M, Xu K, Ng YS, Wardemann H, Albesiano E, Messmer BT, et al. Unmutated and mutated chronic lymphocytic leukemias derive from self-reactive B cell precursors despite expressing different antibody reactivity. J Clin Invest 2005;115:1636-43. (Pubitemid 40814672)
29. Lanemo Myhrinder A, Hellqvist E, Sidorova E, Soderberg A, Baxendale H, Dahle C, et al. A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies. Blood 2008;111:3838-48.
30. Kostareli E, Hadzidimitriou A, Stavroyianni N, Darzentas N, Athanasiadou A, Gounari M, et al. Molecular evidence for EBV and CMV persistence in a subset of patients with chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors. Leukemia 2009;23:919-24.
31. KatayamaY, Sakai A, Katsutani S, Takimoto Y, Kimura A. Lack of allelic exclusion and isotype switching in B cell chronic lymphocytic leukemia. Am J Hematol 2001;68:295-7. (Pubitemid 33108436)
32. Oppezzo P, Magnac C, Bianchi S, Vuillier F, Tiscornia A,Dumas G, et al. 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. Leukemia 2002;16:2438-46. (Pubitemid 36054379)
33. Oppezzo P, Vuillier F, Vasconcelos Y, Dumas G, Magnac C, Payelle-Brogard B, et al. Chronic lymphocytic leukemia B cells expressing AID display dissociation between class switch recombination and somatic hypermutation. Blood 2003;101:4029-32. (Pubitemid 36857882)
34. Geisler CH, Larsen JK, Hansen NE, Hansen MM,Christensen BE, Lund B, et al. Prognostic importance of flowcytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia. Blood 1991;78:1795-802.
35. Potter KN, Mockridge CI, Neville L, Wheatley I, Schenk M, Orchard J, et al. Structural and functional features of the B-cell receptor in IgGpositive chronic lymphocytic leukemia. Clin Cancer Res 2006;12:1672-9.
36. Vardi A, Agathangelidis A, Sutton LA, Chatzouli M, Scarfo L, Mansouri L, et al. IgG-switched CLL has a distinct immunogenetic signature from the common MD variant: ontogenetic implications. Clin Cancer Res 2013;20:323-30.
37. Taylor JJ, Pape KA, Jenkins MK. A germinal center-independent pathway generates unswitched memory B cells early in the primary response. J Exp Med 2012;209:597-606.
38. Kaji T, Ishige A, Hikida M, Taka J, Hijikata A, Kubo M, et al. Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. J ExpMed2012;209:2079-97.
39. Weill JC, Weller S, Reynaud CA. Human marginal zone B cells. Annu Rev Immunol 2009;27:267-85.
40. Chappell CP, Draves KE, Giltiay NV, Clark EA. Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J Exp Med 2012;209:1825-40.
41. Hardy RR. B-1 B cell development. J Immunol 2006;177:2749-54. (Pubitemid 44277787)
42. Griffin DO,Holodick NE, Rothstein TL.Human B1cells in umbilical cord and adult peripheral blood express the novel phenotypeCD20+ CD27+ CD43+ CD70. J Exp Med 2011;208:67-80.
43. Seifert M, Sellmann L, Bloehdorn J, Wein F, Stilgenbauer S, Durig J, et al. Cellular origin and pathophysiology of chronic lymphocytic leukemia. J Exp Med 2012;209:2183-98.
44. Forconi F, Potter KN, Wheatley I, Darzentas N, Sozzi E, Stamatopoulos K, et al. The normal IGHV1-69-derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL. Blood 2010;115:71-7.
45. Fazi C, Scarfo L, Pecciarini L, Cottini F, Dagklis A, Janus A, et al. General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL. Blood 2011;118:6618 -25.
46. Vardi A, Dagklis A, Scarfo L, Jelinek D, Newton D, Bennett F, et al. Immunogenetics shows that not allMBLare equal: the larger the clone, the more similar to CLL. Blood 2013;121:4521-8.
47. Woyach JA, Smucker K, Smith LL, Lozanski A, Zhong Y, Ruppert AS, et al. Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy. Blood 2014;123:1810-7.
48. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014;370:997-1007.
49. Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 2014;369:32-42.