Therapeutic targeting of the BCL6 oncogene for diffuse large B-cell lymphomas

Leukemia and Lymphoma

Volumn 49, Issue 5, 2008, Pages 874-882

  Parekh, Samir ^a   Prive, Gilbert ^b,c   Melnick, Ari ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF TORONTO   (Canada)

^c PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

Lymphoma and Hodgkin disease; Pharmacotherapeutics; Transcription factor changes

Indexed keywords

ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; AZACITIDINE; B LYMPHOCYTE INDUCED MATURATION PROTEIN 1; CALVASCULIN; CAMBINOL; CD40 LIGAND; CHECKPOINT KINASE 1; CYCLIN D2; CYCLIN DEPENDENT KINASE INHIBITOR 1A; DOXORUBICIN; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; HISTONE H2AX; INTERFERON REGULATORY FACTOR 4; MICRORNA; NICOTINAMIDE ADENINE DINUCLEOTIDE; NUCLEAR RECEPTOR COREPRESSOR; PHENYBUTYRATE; PROTEASOME INHIBITOR; PROTEIN BCL 6; PROTEIN P53; RESVERATROL; RETINOIC ACID; SILENCING MEDIATOR OF RETINOID AND THYROID HORMONE RECEPTOR; STAT5 PROTEIN; SUMO 1 PROTEIN; TRICHOSTATIN A;

ACETYLATION; ANTINEOPLASTIC ACTIVITY; B CELL LYMPHOMA; B LYMPHOCYTE; CELL CYCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; DNA DAMAGE; DOWN REGULATION; DRUG DESIGN; DRUG POTENTIATION; DRUG TARGETING; GENE CONTROL; GENE EXPRESSION REGULATION; GENE REPRESSION; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOMIC INSTABILITY; GERMINAL CENTER; HUMAN; LARGE CELL LYMPHOMA; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; REVIEW;

EID: 46749154664     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.1080/10428190801895345     Document Type: Review

References (59)

1. Melnick, A. and Licht, J. D. (1999) Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood, 93, pp. 3167-3215.
2. Dent, A. L., Shaffer, A. L., Yu, X., Allman, D. and Staudt, L. M. (1997) Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science, 276, pp. 589-592.
3. Ye, B. H., Cattoretti, G., Shen, Q., Zhang, J., Hawe, N. and de Waard, R. (1997) The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation. Nat Genet, 16, pp. 161-170.
4. Tunyaplin, C., Shaffer, A. L., Angelin-Duclos, C. D., Yu, X., Staudt, L. M. and Calame, K. L. (2004) Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation. J Immunol, 173, pp. 1158-1165.
5. Kuo, T. C., Shaffer, A. L., Haddad, J., Choi Jr, Y. S., Staudt, L. M. and Calame, K. (2007) Repression of BCL-6 is required for the formation of human memory B cells in vitro. J Exp Med, 204, pp. 819-830.
6. Shaffer, A. L., Yu, X., He, Y., Boldrick, J., Chan, E. P. and Staudt, L. M. (2000) BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity, 13, pp. 199-212.
7. Reljic, R., Wagner, S. D., Peakman, L. J. and Fearon, D. T. (2000) Suppression of signal transducer and activator of transcription 3-dependent B lymphocyte terminal differentiation by BCL-6. J Exp Med, 192, pp. 1841-1848.
8. Allen, C. D., Okada, T. and Cyster, J. G. (2007) Germinal-center organization and cellular dynamics. Immunity, 27, pp. 190-202.
9. Okazaki, I. M., Kotani, A. and Honjo, T. (2007) Role of AID in tumourigenesis. Adv Immunol, 94, pp. 245-273.
10. Pasqualucci, L., Neumeister, P., Goossens, T., Nanjangud, G., Chaganti, R. S. and Kuppers, R. (2001) Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature, 412, pp. 341-346.
11. Spencer, J. O. and Dunn-Walters, D. K. (1999) Somatic hypermutation and B-cell malignancies. J Pathol, 187, pp. 158-163.
12. Pasqualucci, L., Bereschenko, O., Niu, H., Klein, U., Basso, K. and Guglielmino, R. (2003) Molecular pathogenesis of non-Hodgkin's lymphoma: the role of Bcl-6. Leuk Lymphoma, 44, pp. S5-S12.
13. Cattoretti, G., Pasqualucci, L., Ballon, G., Tam, W., Nandula, S. V. and Shen, Q. (2005) Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice. Cancer Cell, 7, pp. 445-455.
14. Baron, B. W., Anastasi, J., Montag, A., Huo, D., Baron, R. M. and Karrison, T. (2004) The human BCL6 transgene promotes the development of lymphomas in the mouse. Proc Natl Acad Sci USA, 101, pp. 14198-14203.
15. Polo, J. M., Juszczynski, P., Monti, S., Cerchietti, L., Ye, K. and Greally, J. M. (2007) Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas. Proc Natl Acad Sci USA, 104, pp. 3207-3212.
16. Ranuncolo, S. M., Polo, J. M., Dierov, J., Singer, M., Kuo, T. and Greally, J. (2007) Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR. Nat Immunol, 8, pp. 705-714.
17. Phan, R. T. and Dalla-Favera, R. (2004) The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature, 432, pp. 635-639.
18. Phan, R. T., Saito, M., Basso, K., Niu, H. and Dalla-Favera, R. (2005) BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells. Nat Immunol, 6, pp. 1054-1060.
19. Wright, J. A., Keegan, K. S., Herendeen, D. R., Bentley, N. J., Carr, A. M. and Hoekstra, M. F. (1998) Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control. Proc Natl Acad Sci USA, 95, pp. 7445-7450.
20. Cuadrado, M., Martinez-Pastor, B., Murga, M., Toledo, L. I., Gutierrez-Martinez, P. and Lopez, E. (2006) ATM regulates ATR chromatin loading in response to DNA double-strand breaks. J Exp Med, 203, pp. 297-303.
21. Petermann, E. and Caldecott, K. W. (2006) Evidence that the ATR/Chk1 pathway maintains normal replication fork progression during unperturbed S phase. Cell Cycle, 5, pp. 2203-2209.
22. Ward, I. M. and Chen, J. (2001) Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem, 276, pp. 47759-47762.
23. Liu, Q., Guntuku, S., Cui, X. S., Matsuoka, S., Cortez, D. and Tamai, K. (2000) Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev, 14, pp. 1448-1459.
24. Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M. and Bartek, J. (2000) Rapid destruction of human Cdc25A in response to DNA damage. Science, 288, pp. 1425-1429.
25. Shieh, S. Y., Ahn, J., Tamai, K., Taya, Y. and Prives, C. (2000) The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev, 14, pp. 289-300.
26. Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z. and Piwnica-Worms, H. (1997) Conservation of the Chk1 checkpoint pathway in mammals: Linkage of DNA damage to Cdk regulation through Cdc25. Science, 277, pp. 1497-1501.
27. Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A. and Shieh, S. Y. (1999) A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev, 13, pp. 152-157.
28. Phan, R. T., Saito, M., Kitagawa, Y., Means, A. R. and Dalla-Favera, R. (2007) Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells. Nat Immunol, 8, pp. 1132-1139.
29. Parekh, S., Polo, J. M., Shaknovich, R., Juszczynski, P., Lev, P. and Ranuncolo, S. M. (2007) BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms. Blood, 110, pp. 2067-2074.
30. Vasanwala, F. H., Kusam, S., Toney, L. M. and Dent, A. L. (2002) Repression of AP-1 function: A mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene. J Immunol, 169, pp. 1922-1929.
31. Shaffer, A. L., Lin, K. I., Kuo, T. C., Yu, X., Hurt, E. M. and Rosenwald, A. (2002) Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity, 17, pp. 51-62.
32. Allen, C. D., Okada, T., Tang, H. L. and Cyster, J. G. (2007) Imaging of germinal center selection events during affinity maturation. Science, 315, pp. 528-531.
33. Saito, M., Gao, J., Basso, K., Kitagawa, Y., Smith, P. M. and Bhagat, G. (2007) A signalling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma. Cancer Cell, 12, pp. 280-292.
34. Walker, S. R., Nelson, E. A. and Frank, D. A. (2007) STAT5 represses BCL6 expression by binding to a regulatory region frequently mutated in lymphomas. Oncogene, 26, pp. 224-233.
35. Chang, C. C., Ye, B. H., Chaganti, R. S. and Dalla-Favera, R. (1996) BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. Proc Natl Acad Sci USA, 93, pp. 6947-6952.
36. Ahmad, K. F., Melnick, A., Lax, S., Bouchard, D., Liu, J. and Kiang, C. L. (2003) Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain. Mol Cell, 12, pp. 1551-1564.
37. Huynh, K. D. and Bardwell, V. J. (1998) The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT. Oncogene, 17, pp. 2473-2484.
38. Huynh, K. D., Fischle, W., Verdin, E. and Bardwell, V. J. (2000) BCoR, a novel corepressor involved in BCL-6 repression. Genes Dev, 14, pp. 1810-1823.
39. Stogios, P. J., Chen, L. and Prive, G. G. (2007) Crystal structure of the BTB domain from the LRF/ZBTB7 transcriptional regulator. Protein Sci, 16, pp. 336-342.
40. Prive, G. G. and Melnick, A. (2006) Specific peptides for the therapeutic targeting of oncogenes. Curr Opin Genet Dev, 16, pp. 71-77.
41. Polo, J. M., Dell'Oso, T., Ranuncolo, S. M., Cerchietti, L., Beck, D. and Da Silva, G. F. (2004) Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells. Nat Med, 10, pp. 1329-1335.
42. Cerchietti, L., Polo, J., DaSilva, G., Dowdy, S., Cattoretti, G. and Shaknovich, R. (2005) BCL6, p53 and Molecular Targeted Therapy in B-Cell Lymphomas. Blood, 106:427
43. Stogios, P. J., Downs, G. S., Jauhal, J. J., Nandra, S. K. and Prive, G. G. (2005) Sequence and structural analysis of BTB domain proteins. Genome Biol, 6, p. R82.
44. Ahmad, K. F., Engel, C. K. and Prive, G. G. (1998) Crystal structure of the BTB domain from PLZF. Proc Natl Acad Sci USA, 95, pp. 12123-12128.
45. Melnick, A., Carlile, G., Ahmad, K. F., Kiang, C. L., Corcoran, C. and Bardwell, V. (2002) Critical residues within the BTB domain of PLZF and Bcl-6 modulate interaction with corepressors. Mol Cell Biol, 22, pp. 1804-1818.
46. Chattopadhyay, A., Tate, S. A., Beswick, R. W., Wagner, S. D. and Ko Ferrigno, P (2006) A peptide aptamer to antagonize BCL-6 function. Oncogene, 25, pp. 2223-2233.
47. Fujita, N., Jaye, D. L., Geigerman, C., Akyildiz, A., Mooney, M. R. and Boss, J. M. (2004) MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation. Cell, 119, pp. 75-86.
48. Chevallier, N., Corcoran, C. M., Lennon, C., Hyjek, E., Chadburn, A. and Bardwell, V. J. (2004) ETO protein of t(8;21) AML is a corepressor for Bcl-6 B-cell lymphoma oncoprotein. Blood, 103, pp. 1454-1463.
49. Miles, R. R., Crockett, D. K., Lim, M. S. and Elenitoba-Johnson, K. S. (2005) Analysis of BCL6-interacting proteins by tandem mass spectrometry. Mol Cell Proteomics, 4, pp. 1898-1909.
50. Bereshchenko, O. R., Gu, W. and Dalla-Favera, R. (2002) Acetylation inactivates the transcriptional repressor BCL6. Nat Genet, 32, pp. 606-613.
51. Li, J., Wang, J., Nawaz, Z., Liu, J. M., Qin, J. and Wong, J. (2000) Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. Embo J, 19, pp. 4342-4350.
52. Sakajiri, S., Kumagai, T., Kawamata, N., Saitoh, T., Said, J. W. and Koeffler, H. P. (2005) Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines. Exp Hematol, 33, pp. 53-61.
53. Heltweg, B., Gatbonton, T., Schuler, A. D., Posakony, J., Li, H. and Goehle, S. (2006) Antitumour activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res, 66, pp. 4368-4377.
54. Kalota, A. and Opalinska, J. B. (2007) Design of antisense oligonucleotides and short interfering RNA duplexes (siRNA) targeted to BCL6 mRNA: Towards rational drug development for specific lymphoma subsets. Blood Cells Mol Dis, 38, pp. 199-203.
55. Saito, Y., Liang, G., Egger, G., Friedman, J. M., Chuang, J. C. and Coetzee, G. A. (2006) Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell, 9, pp. 435-443.
56. Alizadeh, A. A., Eisen, M. B., Davis, R. E., Ma, C., Lossos, I. S. and Rosenwald, A. (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 403, pp. 503-511.
57. Monti, S., Savage, K. J., Kutok, J. L., Feuerhake, F., Kurtin, P. and Mihm, M. (2005) Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood, 105, pp. 1851-1861.
58. Faber, A. C. and Chiles, T. C. (2006) Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: Evidence for a novel mechanism involving inhibition of BCL6 signalling. Int J Oncol, 29, pp. 1561-1566.
59. Jazirehi, A. R. and Bonavida, B. (2004) Resveratrol modifies the expression of apoptotic regulatory proteins and sensitizes non-Hodgkin's lymphoma and multiple myeloma cell lines to paclitaxel-induced apoptosis. Mol Cancer Ther, 3, pp. 71-84.