{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T14:25:55Z","timestamp":1781619955719,"version":"3.54.5"},"reference-count":84,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2014,7,24]],"date-time":"2014-07-24T00:00:00Z","timestamp":1406160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2014,12,15]]},"abstract":"<jats:p>Aberrant expression of the v\u2010myc avian myelocytomatosis viral oncogene homolog (MYC) proto\u2010oncogene has known transformative potential in healthy human cells. Chromosomal MYC rearrangements and consequent MYC overexpression is the defining lesion in Burkitt lymphoma (BL), conferring a highly proliferative state. However, abnormalities of MYC are increasingly appreciated in non\u2010BL histologies, including diffuse large B\u2010cell lymphoma (DLBCL) and B\u2010cell lymphomas intermediate between BL and DLBCL, with a particularly aggressive clinical phenotype. Although there are conflicting data regarding prognostic implications of isolated MYC aberrancy in these non\u2010BLs, the co\u2010occurrence of <jats:italic>MYC<\/jats:italic> rearrangements <jats:italic>and<\/jats:italic> either the antiapoptotic gene B\u2010cell chronic lymphocytic leukemia\/lymphoma 2 (<jats:italic>BCL2<\/jats:italic>) or the transcriptional repressor <jats:italic>BCL6<\/jats:italic> leads to an entity termed <jats:italic>double\u2010hit<\/jats:italic> B\u2010cell lymphoma (DHL) (or <jats:italic>triple\u2010hit<\/jats:italic> if all 3 abnormalities are observed) with a particularly poor prognosis and no established treatment paradigms. Notably, a distinct pattern of gene expression profiling has been noted when <jats:italic>MYC<\/jats:italic> is overexpressed in BL compared with other lymphomas, supporting the notion that, although <jats:italic>MYC<\/jats:italic> promotes target gene transcription, the target genes vary by disease subtype. The frequency of <jats:italic>MYC<\/jats:italic> activity depends on the method of detection and ranges from 5% to 10% using fluorescence in situ hybridization but up to 30% of DLBCL using immunohistochemistry. Standard therapies developed for DLBCL are less effective when the disease is driven by <jats:italic>MYC<\/jats:italic>, leading to lower response rates and response durations. An important clinical challenge is to pre\u2010emptively identify MYC\u2010associated lymphomas and to subsequently develop trials specifically for this group of patients. However, the design of such studies is complicated by variable definitions of <jats:italic>MYC<\/jats:italic>\u2010associated lymphoid malignancies and the lack of effective therapies to date. The objective if the current review was to evaluate the implications of <jats:italic>MYC<\/jats:italic> aberrancy with respect to the B\u2010cell lymphoma double\u2010hit and triple\u2010hit phenotypes and to consider the available data for clinical and practical management. <jats:bold><jats:italic>Cancer<\/jats:italic> 2014;120:3884\u20133895.<\/jats:bold> \u00a9 <jats:italic>2014 American Cancer Society<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/cncr.28899","type":"journal-article","created":{"date-parts":[[2014,7,24]],"date-time":"2014-07-24T12:29:29Z","timestamp":1406204969000},"page":"3884-3895","source":"Crossref","is-referenced-by-count":81,"title":["MYC\u2010associated and double\u2010hit lymphomas: A review of pathobiology, prognosis, and therapeutic approaches"],"prefix":"10.1002","volume":"120","author":[{"given":"Adam M.","family":"Petrich","sequence":"first","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chadi","family":"Nabhan","sequence":"additional","affiliation":[{"name":"The University of Chicago Pritzker School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali M.","family":"Smith","sequence":"additional","affiliation":[{"name":"The University of Chicago Pritzker School of Medicine Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,24]]},"reference":[{"key":"e_1_2_4_2_1","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow 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Novel combinations of CC\u2010122 CC\u2010223 CC\u2010292 and rituximab in diffuse large B\u2010cell lymphoma.ClinicalTrials.govIdentifier NCT02031419. Available at:http:\/\/clinicaltrials.gov\/ct2\/show\/NCT02031419?term=cc122+cc223+cc292&rank=1"},{"key":"e_1_2_4_79_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-538546"},{"key":"e_1_2_4_80_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-537555"},{"key":"e_1_2_4_81_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315226"},{"key":"e_1_2_4_82_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-181008"},{"issue":"1","key":"e_1_2_4_83_1","first-page":"96","article-title":"The novel 2nd generation proteasome inhibitor MLN9708 induces redox\u2010 and MAPK\u2010related cell death in T\u2010cell lymphoma (TCL) and Hodgkin lymphoma (HL) cell lines and human lymphoma xenograft models","volume":"31","author":"Evens AM","year":"2013","journal-title":"Hematol Oncol"},{"key":"e_1_2_4_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.036"},{"key":"e_1_2_4_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201202034"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.28899","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.28899","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T13:46:44Z","timestamp":1760276804000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.28899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,24]]},"references-count":84,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2014,12,15]]}},"alternative-id":["10.1002\/cncr.28899"],"URL":"https:\/\/doi.org\/10.1002\/cncr.28899","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,24]]}}}