Hemophagocytic lymphohistiocytosis with MUNC13-4 gene mutation or reduced natural killer cell function prior to onset of childhood leukemia

Hemophagocytic lymphohistiocytosis (HLH) is a rare histiocytic reactive process due to mutations in the perforin, MUNC13‐4 or syntaxin 11 genes, or secondary to malignancy, infection or autoimmune disorder. HLH as a preceding diagnosis to leukemia is rare. We report two cases with progression to acute leukemia, one heterozygous for MUNC13‐4 and the other with reduced natural killer (NK) cell function and perforin expression. These defects may predispose to a secondary HLH‐like presentation of pre‐clinical leukemia or confer increased susceptibility to malignancy. HLH patients with genetic mutations or NK cell function abnormalities need monitoring for future malignancy even if the HLH resolves. Pediatr Blood Cancer 2011;56:856–858. © 2010 Wiley‐Liss, Inc.