Gene-expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis

We performed gene-expression profiling of PBMCs obtained from patients with familial hemophagocytic lymphohistiocytosis (FHL) to screen for biologic correlates with the genetic and/or clinical forms of this disease. Unsupervised hierarchical clustering of 167 differentially expressed probe sets, rep...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2013-02, Vol.121 (7), p.e14-e24
Main Authors: Sumegi, Janos, Nestheide, Shawnagay V., Barnes, Michael G., Villanueva, Joyce, Zhang, Kejian, Grom, Alexei A., Filipovich, Alexandra H.
Format: Article
Language:English
Subjects:
Adolescent
Age of Onset
Case-Control Studies
Child
Child, Preschool
Cohort Studies
Disease Progression
Gene Expression Profiling
Humans
Immunobiology
Infant
Lymphohistiocytosis, Hemophagocytic - classification
Lymphohistiocytosis, Hemophagocytic - genetics
Lymphohistiocytosis, Hemophagocytic - immunology
Lymphoid Neoplasia
Multigene Family
Mutation
Myeloid Neoplasia
Pediatric Hematology
Perforin
Pore Forming Cytotoxic Proteins - deficiency
Pore Forming Cytotoxic Proteins - genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We performed gene-expression profiling of PBMCs obtained from patients with familial hemophagocytic lymphohistiocytosis (FHL) to screen for biologic correlates with the genetic and/or clinical forms of this disease. Unsupervised hierarchical clustering of 167 differentially expressed probe sets, representing 143 genes, identified 3 groups of patients corresponding to the genetic forms and clinical presentations of the disease. Two clusters of up- and down-regulated genes separated patients with perforin-deficient FHL from those with unidentified genetic cause(s) of the disease. The clusterscomprised genes involved in defense/immune responses, apoptosis, zinc homeostasis, and systemic inflammation. Unsupervised hierarchical clustering partitioned patients with unknown genetic cause(s) of FHL into 2 well-distinguished subgroups. Patterns of up- and down-regulated genes separated patients with “late-onset” and “relapsing” forms of FHL from patients with an “early onset and rapidly evolving” form of the disease. A cluster was identified in patients with “late onset and relapsing” form of FHL related to B- and T-cell differentiation/survival, T-cell activation, and vesicular transport. The resulting data suggest that unique gene-expression signatures can distinguish between genetic and clinical subtypes of FHL. These differentially expressed genes may represent biomarkers that can be used as predictors of disease progression. •Distinct gene expression signatures are associated with genetic and clinical subtypes of hemophagocytic lymphohistiocytosis.
ISSN:0006-4971
1528-0020
1528-0020
DOI:10.1182/blood-2012-05-425769