MYC-associated and double-hit lymphomas: A review of pathobiology, prognosis, and therapeutic approaches

Cancer

Volumn 120, Issue 24, 2014, Pages 3884-3895

  Petrich, Adam M ^a   Nabhan, Chadi ^b   Smith, Sonali M ^b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

Author keywords

Aggressive lymphoma; BCL2; Double hit; Lymphoma; MYC

Indexed keywords

ALISERTIB; MYC PROTEIN; NAVITOCLAX; BCL6 PROTEIN, HUMAN; DNA BINDING PROTEIN; MYC PROTEIN, HUMAN; PROTEIN BCL 2;

B CELL LYMPHOMA; CANCER PROGNOSIS; CANCER THERAPY; CARCINOGENESIS; DISEASE ASSOCIATION; DOUBLE HIT LYMPHOMA; DRUG TARGETING; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; LYMPHOMA; MANAGED CARE; MOLECULAR PATHOLOGY; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; CELL TRANSFORMATION; GENETICS; LYMPHOMA, B-CELL; PATHOLOGY; PROGNOSIS;

CELL TRANSFORMATION, NEOPLASTIC; DNA-BINDING PROTEINS; HUMANS; LYMPHOMA, B-CELL; PROGNOSIS; PROTO-ONCOGENE PROTEINS C-BCL-2; PROTO-ONCOGENE PROTEINS C-MYC;

EID: 84919391569     PISSN: 0008543X     EISSN: 10970142     Source Type: Journal    
DOI: 10.1002/cncr.28899     Document Type: Review

References (84)

1. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008.
2. Alitalo K, Bishop JM, Smith DH, Chen EY, Colby WW, Levinson AD. Nucleotide sequence to the v-myc oncogene of avian retrovirus MC29. Proc Natl Acad Sci U S A. 1983; 80: 100-104.
3. Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A 1982; 79: 7824-7827.
4. Fernandez, PC, Frank SR, Wang L, et al. Genomic targets of the human c-Myc protein. Genes Dev. 2003; 7: 1115-2229.
5. Eilers MS, Schirm S, Bishop JM. The MYC protein activates transcription of the alpha-prothymosin gene. EMBO J. 1991; 10: 133-141.
6. Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol. 2005; 6: 635-645.
7. Mateyak MK, Obaya AJ, Sedivy JM. c-Myc regulates cyclin D-Cdk4 and -Cdk6 activity but affects cell cycle progression at multiple independent points. Mol Cell Biol. 1999; 19: 4672-4683.
8. Grandori C, Cowley SM, James LP, Eisenman RN. The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol. 2000; 16: 653-699.
9. Keller UB, Old JB, Dorsey FC, et al. Myc targets Cks1 to provoke the suppression of p27Kip1, proliferation and lymphomagenesis. EMBO J. 2007; 26: 2562-2574.
10. Klapproth K, Wirth T. Advances in the understanding of MYCinduced lymphomagenesis. Br J Haematol. 2010; 149: 484-497.
11. Hermeking H, Eick D. Mediation of c-Myc-induced apoptosis by p53. Science. 1994; 265: 2091-2093.
12. Eischen CM, Woo D, Roussel MF, Cleveland JL. Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis. Mol Cell Biol. 2001; 21: 5063-5070.
13. Chang TC, Yu D, Lee YS, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2008; 40: 43-50.
14. Sander, S, Bullinger L, Wirth T. Repressing the repressor: a new mode of MYC action in lymphomagenesis. Cell Cycle. 2009; 8: 556-559.
15. Yancopoulos GD, Nisen PD, Tesfaye A, Kohl NE, Goldfarb MP, Alt FW. N-myc can cooperate with ras to transform normal cells in culture. Proc Natl Acad Sci U S A. 1985; 82: 5455-5459.
16. Lombardi L, Newcomb EW, Dalla-Favera r. Pathogenesis of Burkitt lymphoma: expression of an activated c-myc oncogene causes the tumorigenic conversion of EBV-infected human B lymphoblasts. Cell. 1987; 49: 161-170.
17. Bieging KT, Amick AC, Longnecker R. Epstein-Barr virus LMP2A bypasses p53 inactivation in an MYC model of lymphomagenesis. Proc Natl Acad Sci U S A. 2009; 106: 17945-17950.
18. Cole MD, Cowling VH. Transcription-independent functions of MYC: regulation of translation and DNA replication. Nat Rev Mol Cell Biol. 2008; 9: 810-815.
19. Cowling VH. Myc up-regulates formation of the mRNA methyl cap. Biochem Soc Trans. 2010; 38: 1598-1601.
20. Dominguez-Sola D, Ying CY, Grandori C, et al. Non-transcriptional control of DNA replication by c-Myc. Nature. 2007; 448: 445-451.
21. Mason KD, Vandenberg CJ, Scott CL, et al. In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas. Proc Natl Acad Sci U S A. 2008; 105: 17961-17966.
22. Kluk MJ, Chapuy B, Sinha P, et al. Immunohistochemical detection of MYC-driven diffuse large B-cell lymphomas [serial online]. PLoS One. 2012; 7: e33813.
23. Ott G, Rosenwald A, Campo E. Understanding MYC driven aggressive B-cell lymphomas: pathogenesis and classification. Blood. 2013; 122: 3884-3891.
24. Dave SS, Fu K, Wright GW, et al; Lymphoma/Leukemia Molecular Profiling Project. Molecular diagnosis of Burkitt's lymphoma. N Engl J Med. 2006; 354: 2431-2442.
25. Niitsu N, Okamoto M, Miura I, Hirano M. Clinical features and prognosis of de novo diffuse large B-cell lymphoma with t(14; 18) and 8q24/c-MYC translocations. Leukemia. 2009; 23: 777-783.
26. Savage KJ, Johnson NA, Ben-Neriah S, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood. 2009; 114: 3533-3537.
27. Barrans S, Crouch S, Smith A, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010; 28: 3360-3365.
28. Horn H, Ziepert M, Becher C, et al; German High-Grade Non- Hodgkin Lymphoma Study Group. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 2013; 121: 2253-2263.
29. Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012; 30: 3452-3459.
30. Stasik CJ, Nitta H, Zhang W, et al. Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma. Haematologica. 2010; 95: 597-603.
31. Pouryazdanparast P, Brenner A, Haghighat Z, Guitart J, Rademaker A, Gerami P. The role of 8q24 copy number gains and c-MYC expression in amelanotic cutaneous melanoma. Mod Pathol. 2012; 25: 1221-1226.
32. Zafarana G, Ishkanian AS, Malloff CA, et al. Copy number alterations of c-MYC and PTEN are prognostic factors for relapse after prostate cancer radiotherapy. Cancer. 2012; 118: 4053-4062.
33. Takei H, Nguyen Y, Mehta V, Chintagumpala M, Dauser RC, Adesina AM. Low-level copy gain versus amplification of myc oncogenes in medulloblastoma: utility in predicting prognosis and survival. Laboratory investigation. J Neurosurg Pediatr. 2009; 3: 61-65.
34. Yoon SO, Jeon YK, Paik JH, et al. MYC translocation and an increased copy number predict poor prognosis in adult diffuse large B-cell lymphoma (DLBCL), especially in germinal centre-like B cell (GCB) type. Histopathology. 2008; 53: 205-217.
35. Testoni M, Kwee I, Greiner TC, et al. Gains of MYC locus and outcome in patients with diffuse large B-cell lymphoma treated with R-CHOP. Br J Haematol. 2011; 155: 274-277.
36. Visscher DW, Wallis T, Awussah S, Mohamed A, Crissman JD. Evaluation of MYC and chromosome 8 copy number in breast carcinoma by interphase cytogenetics. Genes Chromosomes Cancer. 1997; 18: 1-7.
37. Valera A, Lopez-Guuillermo A, Cardesa-Salzman T, et al; Grup per l'Estudi dels Limfomes de Catalunya i Balears (GELCAG). MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Haematologica. 2013; 98: 1554-1562.
38. Mossafa H, et al. Non-Hodgkin's lymphomas with Burkitt-like cells are associated with c-Myc amplification and poor prognosis. Leuk Lymphoma. 2006; 47: 1885-1893.
39. Johnson NA, Savage KJ, Ludkovski O, et al. Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival. Blood. 2009; 114: 2273-2279.
40. van Imhoff GW, Boerma EJ, van der Holt B, et al. Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma. J Clin Oncol. 2006; 24: 4135-4142.
41. Copie-Bergman C, Gaulard P, Leroy K, et al. Immuno-fluorescence in situ hybridization index predicts survival in patients with diffuse large B-cell lymphoma treated with R-CHOP: a GELA study. J Clin Oncol. 2009; 27: 5573-5579.
42. Tibiletti MG, Marti V, Bernasconi B, et al. BCL2, BCL6, MYC, MALT 1, and BCL10 rearrangements in nodal diffuse large B-cell lymphomas: a multicenter evaluation of a new set of fluorescent in situ hybridization probes and correlation with clinical outcome. Hum Pathol. 2009; 40: 645-652.
43. Obermann EC, Csato M, Dirnhofer S, Tzankov A. Aberrations of the MYC gene in unselected cases of diffuse large B-cell lymphoma are rare and unpredictable by morphological or immunohistochemical assessment. J Clin Pathol. 2009; 62: 754-756.
44. Tapia G, Lopez R, Munoz-Marmol AM, et al. Immunohistochemical detection of MYC protein correlates with MYC gene status in aggressive B cell lymphomas. Histopathology. 2011; 59: 672-678.
45. Green TM, Nielsen O, de Stricker K, Xu-Monette ZY, Young KH, Moller MB. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. Am J Surg Pathol. 2012; 36: 612-619.
46. Cuccuini W, Briere J, Mounier N, et al. MYC1 diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation. Blood. 2012; 119: 4619-4624.
47. Caponetti GC, Dave BJ, Smith L, et al. Clinical relevance of MYC, BCL2 and BCL6 rearrangements in diffuse large B-cell lymphoma [abstract]. Hematol Oncol. 2013; 31(suppl 1): 151-200. Abstract 179.
48. Wang XJ, Reddy NM, Li Shaoying. MYC gene single hit diffuse large B cell lymphoma behaves similarly to MYC/BCL2 double hit lymphoma and needs similar aggressive treatment [abstract]. Blood (ASH Annual Meeting Abstracts). 2013; 122: 4313.
49. Howlett C, Goy A, Zielonka T, et al. Dose intensive induction followed by allogeneic stem cell transplantation more than doubles progression-free and overall survival in "double-hit" lymphoma (DHL) [abstract]. Blood (ASH Annual Meeting Abstracts). 2013; 122: 2141.
50. Tsai J, Greer JP, Morgan DS, Li S, Reddy NM. Role of aggressive chemotherapeutic regimens in double hit lymphoma-can alternate aggressive induction regimens overcome the poor prognosis of diffuse large B cell lymphoma [abstract]? Blood (ASH Annual Meeting Abstracts). 2013; 122: 4361.
51. Landsburg DJ, Nasta SD, Svoboda J, Morrissette JJD, Schuster SJ. "Double-hit" cytogenetic status is not predicted by baseline clinicopathologic characteristics and is highly associated with overall survival in B cell lymphoma patients [abstract]. Blood (ASH Annual Meeting Abstracts). 2013; 122; 4338.
52. Hu S, Xu-Monette ZY, Tzankov A, et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from the International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013; 121: 4021- 4031; quiz 4250.
53. Molina TJ, Briere J, Copie-Bergman C, et al. Overexpression of MYC, BCL2, MYC/BCL2, IGM, and non-GC-like immunophenotype predicts a worse PFS and OS in a series of 670 de novo DLBCL: a LYSA study [abstract]. Hematol Oncol. 2013; 31(suppl 1): 151-200. Abstract 178.
54. Pedersen MO, Gang AO, Poulsen TS, et al. MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations. Eur J Haematol. 2014; 92: 42-48.
55. Aukema SM, Siebert R, Schuuring E, et al. Double-hit B-cell lymphomas. Blood. 2011; 117: 2319-2331.
56. Gandhi MK, Petrich AM, Cassaday RD, et al. Impact of induction regimen and consolidative stem cell transplantation in patients with double hit lymphoma (DHL): a large multicenter retrospective analysis [abstract]. Blood (ASH Annual Meeting Abstracts). 2013; 122: 640.
57. Perry AM, Alvarado-Bernal Y, Laurini JA, et al. MYC and BCL2 protein expression predicts survival in patients with diffuse large Bcell lymphoma treated with rituximab. Br J Haematol. 2014; 165: 382-391.
58. Green TM, Young KH, Visco C, et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012; 30: 3460-3467.
59. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403: 503-511.
60. Shipp MA, Ross KN, Tamayo P, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002; 8: 68-74.
61. Rosenwald A, Wright G, Chan WC, et al; Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002; 346: 1937-1947.
62. Fu K, Weisenburger DD, Choi WW, et al. Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol. 2008; 26: 4587-4594.
63. Lenz G, Wright G, Dave SS, et al; Lymphoma/Leukemia Molecular Profiling Project. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008; 359: 2313-2323.
64. Li S, Lin P, Fayad LE, et al. B-cell lymphomas with MYC/8q24 rearrangements and IGH@BCL2/t(14; 18)(q32; q21): an aggressive disease with heterogeneous histology, germinal center B-cell immunophenotype and poor outcome. Mod Pathol. 2012; 25: 145-156.
65. Abramson JS, Barnes JA, Feng Y, et al. Double hit lymphomas: evaluation of prognostic factors and impact of therapy [abstract]. Blood (ASH Annual Meeting Abstracts). 2012; 120: 1619.
66. Haowei S, Savage KJ, Karsan A, et al. Outcome of patients with double-hit lymphomas treated with CODOX-M/IVAC1R followed by hematopoietic stem cell transplantation in British Columbia [abstract]. Blood (ASH Annual Meeting Abstracts). 2013; 122: 1788.
67. Oki Y, Noorani M, Davis RE, et al. Double hit lymphoma: MD Anderson experience [abstract]. Blood (ASH Annual Meeting Abstracts). 2013; 122: 1776.
68. Greenwood M, Armytage T, Fay K, et al. Outcomes of allogeneic SCT for NHL with concurrent MYC and BCL2 translocations: a single centre retrospective analysis [abstract]. Hematol Oncol. 2013; 31(suppl 1): 96-150. Abstract 024.
69. Sasaki N, Kuroda J, Nagoshi H, et al. Bcl-2 is a better therapeutic target than c-Myc, but attacking both could be a more effective treatment strategy for B-cell lymphoma with concurrent Bcl-2 and c- Myc overexpression. Exp Hematol. 2011; 39: 817-828.e1.
70. Vandenberg CJ, Cory S. ABT-199, a new Bcl-2-specific BH3 mimetic, has in vivo efficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia. Blood. 2013; 121: 2285-2288.
71. Davids M. Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) [abstract]. J Clin Oncol. 2013; 31(suppl); 8520.
72. den Hollander J, Rimpi S, Doherty JR, et al. Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state. Blood. 2010; 116: 1498-1505.
73. Friedberg JW, Mahadevan D, Cebula E, et al. Phase II study of alisertib, a selective aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas. J Clin Oncol. 2014; 32: 44-50.
74. Wall M, Poortinga G, Stanley KL, et al. The mTORC1 inhibitor everolimus prevents and treats El-Myc lymphoma by restoring oncogene-induced senescence. Cancer Discov. 2013; 3: 82-95.
75. Pourdehnad M, Truitt ML, Siddigi IN, Ducker GS, Shokat KM, Ruggero D. Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers. Proc Natl Acad Sci U S A. 2013; 110: 11988-11993.
76. Smith SM, van Besien K, Karrison T, et al. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010; 28: 4740-4746.
77. Celgene Corporation. Novel combinations of CC-122, CC-223, CC-292, and rituximab in diffuse large B-cell lymphoma. Clinical- Trials.gov Identifier NCT02031419. Available at: http://clinicaltrials. gov/ct2/show/NCT02031419?term5cc1221cc2231cc292&rank51
78. Flinn IW, Kahl BS, Leonard JP, et al. Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-delta, as therapy for previously treated indolent non-Hodgkin lymphoma. Blood. 2014; 123: 3406-3413.
79. Kahl BS, Spurgeon SE, Furman RR, et al. Results of a phase I study of idelalisib, a PI3Kd inhibitor, in patients with relapsed or refractory mantle cell lymphoma (MCL) [published online ahead of print March 10, 2014]. Blood. doi: 10.1182/blood-2013-11-537555.
80. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014; 370: 997-1007.
81. Klapproth K, Sander S, Marinkovic D, Baumann B, Wirth T. The IKK2/NF-jB pathway suppresses MYC-induced lymphomagenesis. Blood. 2009; 114: 2448-2558.
82. Evens AM, Dashnamoorthy R, Kandela I, Mazar A. The novel 2nd generation proteasome inhibitor MLN9708 induces redox- and MAPK-related cell death in T-cell lymphoma (TCL) and Hodgkin lymphoma (HL) cell lines and human lymphoma xenograft models. Hematol Oncol. 2013; 31(suppl 1): 96-150. Abstract 030.
83. Loven J, Hoke HA, Lin CY, et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell. 2013; 153: 320-334.
84. Emadali A, Rousseaux S, Bruder-Costa J, et al. Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls rituximab response and tumour growth in aggressive lymphoid cancers. EMBO Mol Med. 2013; 5: 1180-1195.