MYC‐associated and double‐hit lymphomas: A review of pathobiology, prognosis, and therapeutic approaches. Issue 24 (24th July 2014)

• Record Type: Journal Article
• Authors: Petrich, Adam M.; Nabhan, Chadi; Smith, Sonali M.
• Is Part Of: Cancer. Volume 120:Issue 24(2014)
• Page Start: 3884
• Page End: 3895
• Publication Date: 2014-07-24
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28899
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Aberrant expression of the v‐myc avian myelocytomatosis viral oncogene homolog (MYC) proto‐oncogene 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‐BL histologies, including diffuse large B‐cell lymphoma (DLBCL) and B‐cell 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‐BLs, the co‐occurrence of <italic>MYC</italic> rearrangements <italic>and</italic> either the antiapoptotic gene B‐cell chronic lymphocytic leukemia/lymphoma 2 (<italic>BCL2</italic>) or the transcriptional repressor <italic>BCL6</italic> leads to an entity termed <italic>double‐hit</italic> B‐cell lymphoma (DHL) (or <italic>triple‐hit</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 <italic>MYC</italic> is overexpressed in BL compared with other lymphomas, supporting the notion that, although <italic>MYC</italic> promotes target gene transcription, the target genes vary by disease subtype. The frequency of <italic>MYC</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 <italic>MYC</italic>, leading to lower response rates and response durations. An important clinical challenge is to pre‐emptively identify MYC‐associated lymphomas and to subsequently develop trials specifically for this group of patients. However, the design of such studies is complicated by variable definitions of <italic>MYC</italic>‐associated lymphoid malignancies and the lack of effective therapies to date. The objective if the current review was to evaluate the implications of <italic>MYC</italic> aberrancy with respect to the B‐cell lymphoma double‐hit and triple‐hit phenotypes and to consider the available data for clinical and practical management. <bold><italic>Cancer</italic> 2014;120:3884–3895.</bold> © <italic>2014 American Cancer Society</italic>.</p> </abstract>