title: The impact of MYC rearrangements and "double hit" abnormalities in diffuse large B-cell lymphoma.
abstract: Diffuse large B-cell lymphoma (DLBCL) is heterogeneous. Gene expression profiling (GEP) has identified two principal subtypes: germinal center B cell (GCB) and activated B cell (ABC). Most DLBCL cases are distinct from Burkitt lymphoma (BL), but a subset of tumors has a GEP profile between BL and DLBCL, suggesting a spectrum. In parallel, the 2008 World Health Organization (WHO) classification included the category of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (BCL-U). MYC rearrangement and potential synergy with other genetic aberrations, particularly BCL2 or BCL6, so-called double hit lymphoma, have also been studied in DLBCL and gray zone lymphoma. These subsets have been associated with a poor patient outcome, with the data being strongest for MYC/BCL2 double hit lymphomas. This review summarizes the literature on the impact of MYC rearrangement, as well as MYC/BCL2 double hit, in patients with DLBCL and BCL-U. We also emphasize the evolving nature of these concepts, and outline suggestions for future studies.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA. peilin@mdanderson.org
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015321:Gene Rearrangement; D016259:Genes, myc / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation
references.citation: Cell. 2012 Sep 28;151(1):68-79
references.pmid: 23021216
references.citation: Haematologica. 2007 Oct;92(10):1297-301
references.pmid: 18024366
references.citation: Leukemia. 2012 Sep;26(9):2103-13
references.pmid: 22437443
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3433-5
references.pmid: 22949148
references.citation: Nature. 2011 Mar 10;471(7337):189-95
references.pmid: 21390126
references.citation: Hum Pathol. 2009 May;40(5):645-52
references.pmid: 19144384
references.citation: Am J Surg Pathol. 2010 Mar;34(3):327-40
references.pmid: 20118770
references.citation: Leuk Lymphoma. 2013 Oct;54(10):2149-54
references.pmid: 23363269
references.citation: J Clin Exp Hematop. 2012;52(2):113-9
references.pmid: 23037627
references.citation: Histopathology. 2012 Dec;61(6):1214-8
references.pmid: 23171357
references.citation: Br J Haematol. 2013 Jul;162(1):40-9
references.pmid: 23600716
references.citation: Blood. 2012 Apr 19;119(16):3757-66
references.pmid: 22374697
references.citation: Curr Opin Hematol. 2012 Jul;19(4):299-304
references.pmid: 22504522
references.citation: J Clin Oncol. 2011 Nov 1;29(31):4079-87
references.pmid: 21947824
references.citation: N Engl J Med. 2002 Jun 20;346(25):1937-47
references.pmid: 12075054
references.citation: Eur J Haematol. 2012 Jul;89(1):63-71
references.pmid: 22510149
references.citation: Blood. 2013 May 16;121(20):4021-31; quiz 4250
references.pmid: 23449635
references.citation: Nature. 2011 Jul 27;476(7360):298-303
references.pmid: 21796119
references.citation: J Clin Exp Hematop. 2011;51(1):7-12
references.pmid: 21628855
references.citation: J Clin Pathol. 2011 Sep;64(9):802-8
references.pmid: 21593346
references.citation: Blood. 2009 Oct 22;114(17):3533-7
references.pmid: 19704118
references.citation: Blood. 2013 Mar 21;121(12):2253-63
references.pmid: 23335369
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3460-7
references.pmid: 22665537
references.citation: Blood. 2008 Sep 15;112(6):2248-60
references.pmid: 18612102
references.citation: Oncogene. 2013 Feb 21;32(8):1066-1072
references.pmid: 22484426
references.citation: Clin Cancer Res. 2009 Sep 1;15(17):5494-502
references.pmid: 19706817
references.citation: Mod Pathol. 2012 Jan;25(1):145-56
references.pmid: 22002575
references.citation: J Clin Oncol. 2011 Jan 10;29(2):200-7
references.pmid: 21135273
references.citation: Curr Hematol Malig Rep. 2011 Mar;6(1):58-66
references.pmid: 21191675
references.citation: Mod Pathol. 2010 Jul;23(7):909-20
references.pmid: 20348878
references.citation: J Clin Oncol. 2010 Jul 10;28(20):3360-5
references.pmid: 20498406
references.citation: Nat Genet. 2011 Jul 31;43(9):830-7
references.pmid: 21804550
references.citation: Leuk Lymphoma. 2008 Mar;49(3):470-6
references.pmid: 18297523
references.citation: Histopathology. 2012 Nov;61(5):945-54
references.pmid: 22804688
references.citation: Blood. 2012 Nov 22;120(22):4400-6
references.pmid: 23018644
references.citation: Am J Surg Pathol. 2009 Dec;33(12):1815-22
references.pmid: 19816150
references.citation: N Engl J Med. 2006 Jun 8;354(23):2431-42
references.pmid: 16760443
references.citation: Am J Surg Pathol. 2005 Jan;29(1):121-4
references.pmid: 15613866
references.citation: Br J Haematol. 2011 Oct;155(2):274-7
references.pmid: 21488860
references.citation: Cancer. 2012 Mar 15;118(6):1566-73
references.pmid: 21882178
references.citation: Haematologica. 2010 Apr;95(4):597-603
references.pmid: 20378577
references.citation: Blood. 2011 Feb 24;117(8):2319-31
references.pmid: 21119107
references.citation: N Engl J Med. 2006 Jun 8;354(23):2419-30
references.pmid: 16760442
references.citation: Blood. 2009 Sep 10;114(11):2273-9
references.pmid: 19597184
references.citation: Am J Surg Pathol. 2005 Dec;29(12):1652-60
references.pmid: 16327438
references.citation: J Clin Oncol. 2011 May 10;29(14):1835-43
references.pmid: 21482997
references.citation: Leukemia. 2009 Feb;23(2):225-34
references.pmid: 18923440
references.citation: J Clin Pathol. 2011 Nov;64(11):1032-4
references.pmid: 21778297
references.citation: Cancer. 2012 Sep 1;118(17):4173-83
references.pmid: 22213394
references.citation: Hematology Am Soc Hematol Educ Program. 2012;2012:402-9
references.pmid: 23233611
references.citation: Am J Surg Pathol. 2013 Mar;37(3):323-32
references.pmid: 23348205
references.citation: Haematologica. 2007 Oct;92(10):1335-42
references.pmid: 18024371
references.citation: Proc Natl Acad Sci U S A. 1988 Nov;85(22):8548-52
references.pmid: 3186743
references.citation: Haematologica. 2011 Sep;96(9):1327-34
references.pmid: 21659362
references.citation: Leukemia. 2009 Apr;23(4):777-83
references.pmid: 19151788
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3452-9
references.pmid: 22851565
references.citation: Haematologica. 2009 Jul;94(7):935-43
references.pmid: 19535347
references.citation: Blood. 1998 Nov 1;92(9):3152-62
references.pmid: 9787151
references.citation: J Clin Oncol. 1999 May;17(5):1558-67
references.pmid: 10334544
references.citation: Blood. 2012 May 17;119(20):4619-24
references.pmid: 22408263
references.citation: Blood. 2004 Jan 1;103(1):275-82
references.pmid: 14504078
references.citation: J Clin Oncol. 2010 May 10;28(14):2373-80
references.pmid: 20385988
references.citation: Leukemia. 2008 Dec;22(12):2226-9
references.pmid: 18754028
references.citation: Mod Pathol. 2006 Jan;19(1):25-33
references.pmid: 16258503