title: Biology of double-hit B-cell lymphomas.
abstract: OBJECTIVE
  Mature B-cell lymphomas bearing concurrent chromosomal rearrangement of MYC/8q24 and BCL2/18q21 are associated with an aggressive clinical course and resistance to conventional chemotherapy. This review summarizes the recent literature regarding the clinical and pathologic features of double-hit lymphomas and outlines current questions about the most accurate and inclusive definition of the disease.
  
  
  RESULTS
  Comprehensive evaluation of large series of aggressive mature B-cell neoplasms reveals recurrent chromosomal aberrations in the majority of cases. A subset of these lymphomas harbors multiple rearrangements, including MYC/8q24 in combination with BCL2/18q21 and/or BCL6/3q27, and displays a particularly aggressive clinical course. Recent data suggest that consideration of additional features, such as copy number alteration, quantitative protein expression, and biologic pathway activation may be important in deriving a more accurate definition of double-hit lymphoma. Despite the poor prognosis associated with this subset of lymphomas, there remains no evidence for a risk-adapted treatment strategy and no clinical, pathologic, or genetic factors that predict response to therapy.
  
  
  CONCLUSIONS
  Double-hit lymphoma remains an incompletely characterized disease entity. Large, multicenter studies are needed to define relevant clinical, genetic, and pathologic variables and to characterize appropriate risk-adapted treatment strategies.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: R Coleman
authors.initials: RC
authors.lastname: Lindsley
authors.forename: Ann S
authors.initials: AS
authors.lastname: LaCasce
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D050721:Proto-Oncogene Proteins c-cbl