Grants Awarded

Biomarkers in Primary and Secondary Hemophagocytic Lymphohistiocytosis

Principal Investigator
Janos Sumegi MD, PhD
Cincinnati Children’s Hospital Medical Center – Cincinnati, Ohio USA

Date of Award
December 2011

Amount of Award

Layperson Summary
Familial Hemophagocytic Lymphohistiocytosis (HLH) is almost universally fatal unless aggressively treated soon after diagnosis, and corrected with allogeneic bone marrow transplantation. All forms of familial HLH likely result from genetic defects in the natural down regulating mechanisms of immune/inflammatory responses secondary to an impaired cytotoxicity by NK cells and CTLs. HLH results when critical regulatory pathways responsible for the natural termination of immune/inflammatory responses are disrupted or overwhelmed. In HLH, pathologic genetic defects alter normal crosstalk between innate and adaptive immune responses in a manner that compromises homeostatic removal of cells that are superfluous or dangerous to the organism. The purpose of this study is to compare gene expression profiles in peripheral blood mononuclear cells and subsets from patients with active, untreated HLH to define and better understand the pathomechanism of the disease. We hypothesize that gene expression signatures of peripheral blood cells from patients HLH and high-throughput qRT-PCR gene expression methodology will provide new biomarkers for the various forms of the disease. We have already identified unique sets of genes not previously described involved in HLH, and will apply biostatistical methodologies to the genes to generate signature models for primary and secondary hemophagocytic syndrome.

Twelve Month Report


Gene expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis.
Sumegi J, Nestheide SV, Barnes MG, Villanueva J, Zhang K, Grom AA, Filipovich AH.
Blood. 2013 Feb 14;121(7):e14-24. doi: 10.1182/blood-2012-05-425769. Epub 2012 Dec 20.