Double hit and double expressors in lymphoma: Definition and treatment

Cancer. 2018 Dec 15;124(24):4622-4632. doi: 10.1002/cncr.31646. Epub 2018 Sep 25.

Abstract

Emerging biologic subsets and new prognostic markers are significantly and adversely affecting curability after standard chemoimmunotherapy for aggressive B-cell lymphomas. The identification of concurrent MYC and B-cell CLL/lymphoma 2 (BCL2) deregulation, whether at a genomic or protein level, has opened a new era of investigation within the most common subtype of aggressive B-cell lymphomas. Double-hit lymphoma (DHL), defined as a dual rearrangement of MYC and BCL2 and/or B-cell CLL/lymphoma 6 (BCL6) genes, is an uncommon subset accounting for 5% to 7% of all diffuse large B-cell lymphomas (DLBCLs), and long-term survivors are rare. Double-expressor lymphoma (DEL), defined as overexpression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements, is not a distinct entity in the current World Health Organization classification but accounts for 20% to 30% of DLBCL cases and also has poor outcomes. There are many practical considerations related to identifying, determining the prognosis of, and managing DHL and DEL.

Keywords: diffuse large B-cell lymphoma/genetics; diffuse large B-cell lymphoma/pathology; diffuse large B-cell lymphoma/therapy/BCL-2/BCL-6/MYC.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / therapy*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Up-Regulation

Substances

  • BCL2 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc