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

UMMS Affiliation

Department of Pediatrics; Department of Pathology



Document Type


Medical Subject Headings

Child, Preschool; Female; Heterozygote; Humans; Killer Cells, Natural; Leukemia, Monocytic, Acute; Lymphohistiocytosis, Hemophagocytic; Membrane Proteins; Mutation; Perforin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Qa-SNARE Proteins


Hematology | Oncology | Pediatrics


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.

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Citation: 2010 Dec 15. Link to article on publisher's website

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