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

Janos Sumegi, Shawnagay V. Nestheide, Michael G. Barnes, Joyce Villanueva, Kejian Zhang, Alexei A. Grom, Alexandra H. Filipovich

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalBlood
Volume121
Issue number7
DOIs
StatePublished - Feb 14 2013

Fingerprint

Hemophagocytic Lymphohistiocytosis
Transcriptome
Gene expression
Genes
T-cells
Cluster Analysis
Perforin
Biomarkers
T-Lymphocytes
Zinc
Gene Expression Profiling
Chemical activation
Apoptosis
Disease Progression
Cell Differentiation
Cell Survival
Homeostasis
Inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Sumegi, J., Nestheide, S. V., Barnes, M. G., Villanueva, J., Zhang, K., Grom, A. A., & Filipovich, A. H. (2013). Gene-expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis. Blood, 121(7). https://doi.org/10.1182/blood-2012-05-425769

Gene-expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis. / Sumegi, Janos; Nestheide, Shawnagay V.; Barnes, Michael G.; Villanueva, Joyce; Zhang, Kejian; Grom, Alexei A.; Filipovich, Alexandra H.

In: Blood, Vol. 121, No. 7, 14.02.2013.

Research output: Contribution to journalArticle

Sumegi, J, Nestheide, SV, Barnes, MG, Villanueva, J, Zhang, K, Grom, AA & Filipovich, AH 2013, 'Gene-expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis', Blood, vol. 121, no. 7. https://doi.org/10.1182/blood-2012-05-425769
Sumegi, Janos ; Nestheide, Shawnagay V. ; Barnes, Michael G. ; Villanueva, Joyce ; Zhang, Kejian ; Grom, Alexei A. ; Filipovich, Alexandra H. / Gene-expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis. In: Blood. 2013 ; Vol. 121, No. 7.
@article{3e8021fc5ab4429d92cc9e4695cf1a61,
title = "Gene-expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis",
abstract = "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.",
author = "Janos Sumegi and Nestheide, {Shawnagay V.} and Barnes, {Michael G.} and Joyce Villanueva and Kejian Zhang and Grom, {Alexei A.} and Filipovich, {Alexandra H.}",
year = "2013",
month = "2",
day = "14",
doi = "10.1182/blood-2012-05-425769",
language = "English (US)",
volume = "121",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

TY - JOUR

T1 - Gene-expression signatures differ between different clinical forms of familial hemophagocytic lymphohistiocytosis

AU - Sumegi, Janos

AU - Nestheide, Shawnagay V.

AU - Barnes, Michael G.

AU - Villanueva, Joyce

AU - Zhang, Kejian

AU - Grom, Alexei A.

AU - Filipovich, Alexandra H.

PY - 2013/2/14

Y1 - 2013/2/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84874100105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874100105&partnerID=8YFLogxK

U2 - 10.1182/blood-2012-05-425769

DO - 10.1182/blood-2012-05-425769

M3 - Article

VL - 121

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -