Biology of double-hit B-cell lymphomas.

PURPOSE OF REVIEW

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.

RECENT FINDINGS

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.

SUMMARY

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.