Genetic analysis of B-cell lymphomas associated with hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an aggressive, life-threatening syndrome of excessive immune activation. HLH clinically presents with fever, pancytopenia, splenomegaly, and hemophagocytosis in the bone marrow, lymph nodes, or liver. A proposed mechanism for HLH is a paradoxical downregulation of various aspects of the immune response, including B-cell development and function, Toll-like receptor expression and signaling, and apoptosis induction. HLH can be familial or secondary. Secondary HLH is usually associated with infections, rheumatologic disorders, or malignancies. Twentyseven percent of secondary HLH is related to malignancy, the vast majority being hematologic malignancies (HMs), and associated with overall mortality .90%. Yu et al demonstrated that HLH could be an indicator for treatment resistance in patients with lymphoma, especially those of B-cell origin. Chemotherapy may not salvage these patients because of end-organ dysfunction at presentation. B-cell lymphoma–associated HLH may constitute a distinct biological and clinical disease entity that includes specific chromosomal abnormalities. The purpose of this study was to describe the genetic landscape of HM-associated HLH to identify potential targets for clinical trials.