Gene and microRNA analysis of neutrophils from patients with polycythemia vera and essential thrombocytosis

Down-regulation of micro RNA-1 and -133a

Stefanie Slezak, Ping Jin, Lorraine Caruccio, Jiaqiang Ren, Michael Bennett, Nausheen Zia, Sharon Adams, Ena Wang, Joao Ascensao, Geraldine Schechter, David Stroncek

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Since the V617F mutation in JAK2 may not be the initiating event in myeloprofilerative disorders (MPDs) we compared molecular changes in neutrophils from patients with polycythemia vera (PV) and essential thrombocythosis (ET), to neutrophils stimulated by G-CSF administration and to normal unstimulated neutrophils Methods: A gene expression oligonucleotide microarray with more than 35,000 probes and a microRNA (miR) expression array with 827 probes were used to assess neutrophils from 6 MPD patients; 4 with PV and 2 with ET, 5 healthy subjects and 6 healthy subjects given G-CSF. In addition, neutrophil antigen expression was analyzed by flow cytometry and 64 serum protein levels were analyzed by ELISA. Results: Gene expression profiles of neutrophils from the MPD patients were similar but distinct from those of healthy subjects, either unstimulated or G-CSF-mobilized. The differentially expressed genes in MPD neutrophils were more likely to be in pathways involved with inflammation while those of G-CSF-mobilized neutrophils were more likely to belong to metabolic pathways. In MPD neutrophils the expression of CCR1 was increased and that of several NF-κB pathway genes were decreased. MicroRNA miR-133a and miR-1 in MPD neutrophils were down-regulated the most. Levels of 11 serum proteins were increased in MPD patients including MMP-10, MMP-13, VCAM, P-selectin, PDGF-BB and a CCR1 ligand, MIP-1α. Conclusion: These studies showed differential expression of genes particularly involved in inflammatory pathways including the NF-κB pathway and down-regulation of miR-133a and miR-1. These two microRNAs have been previous associated with certain cancers as well as the regulation of hyperthrophy of cardiac and skeletal muscle cells. These changes may contribute to the clinical manifestations of the MPDs.

Original languageEnglish
Article number39
JournalJournal of Translational Medicine
Volume7
DOIs
Publication statusPublished - 4 Jun 2009
Externally publishedYes

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Thrombocytosis
Polycythemia Vera
MicroRNAs
Neutrophils
Down-Regulation
Genes
Granulocyte Colony-Stimulating Factor
Matrix Metalloproteinases
Gene expression
Healthy Volunteers
Blood Proteins
P-Selectin
Flow cytometry
Microarrays
Oligonucleotides
Gene Expression
Muscle
Cells
Metabolic Networks and Pathways
Oligonucleotide Array Sequence Analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gene and microRNA analysis of neutrophils from patients with polycythemia vera and essential thrombocytosis : Down-regulation of micro RNA-1 and -133a. / Slezak, Stefanie; Jin, Ping; Caruccio, Lorraine; Ren, Jiaqiang; Bennett, Michael; Zia, Nausheen; Adams, Sharon; Wang, Ena; Ascensao, Joao; Schechter, Geraldine; Stroncek, David.

In: Journal of Translational Medicine, Vol. 7, 39, 04.06.2009.

Research output: Contribution to journalArticle

Slezak, Stefanie ; Jin, Ping ; Caruccio, Lorraine ; Ren, Jiaqiang ; Bennett, Michael ; Zia, Nausheen ; Adams, Sharon ; Wang, Ena ; Ascensao, Joao ; Schechter, Geraldine ; Stroncek, David. / Gene and microRNA analysis of neutrophils from patients with polycythemia vera and essential thrombocytosis : Down-regulation of micro RNA-1 and -133a. In: Journal of Translational Medicine. 2009 ; Vol. 7.
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T2 - Down-regulation of micro RNA-1 and -133a

AU - Slezak, Stefanie

AU - Jin, Ping

AU - Caruccio, Lorraine

AU - Ren, Jiaqiang

AU - Bennett, Michael

AU - Zia, Nausheen

AU - Adams, Sharon

AU - Wang, Ena

AU - Ascensao, Joao

AU - Schechter, Geraldine

AU - Stroncek, David

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AB - Background: Since the V617F mutation in JAK2 may not be the initiating event in myeloprofilerative disorders (MPDs) we compared molecular changes in neutrophils from patients with polycythemia vera (PV) and essential thrombocythosis (ET), to neutrophils stimulated by G-CSF administration and to normal unstimulated neutrophils Methods: A gene expression oligonucleotide microarray with more than 35,000 probes and a microRNA (miR) expression array with 827 probes were used to assess neutrophils from 6 MPD patients; 4 with PV and 2 with ET, 5 healthy subjects and 6 healthy subjects given G-CSF. In addition, neutrophil antigen expression was analyzed by flow cytometry and 64 serum protein levels were analyzed by ELISA. Results: Gene expression profiles of neutrophils from the MPD patients were similar but distinct from those of healthy subjects, either unstimulated or G-CSF-mobilized. The differentially expressed genes in MPD neutrophils were more likely to be in pathways involved with inflammation while those of G-CSF-mobilized neutrophils were more likely to belong to metabolic pathways. In MPD neutrophils the expression of CCR1 was increased and that of several NF-κB pathway genes were decreased. MicroRNA miR-133a and miR-1 in MPD neutrophils were down-regulated the most. Levels of 11 serum proteins were increased in MPD patients including MMP-10, MMP-13, VCAM, P-selectin, PDGF-BB and a CCR1 ligand, MIP-1α. Conclusion: These studies showed differential expression of genes particularly involved in inflammatory pathways including the NF-κB pathway and down-regulation of miR-133a and miR-1. These two microRNAs have been previous associated with certain cancers as well as the regulation of hyperthrophy of cardiac and skeletal muscle cells. These changes may contribute to the clinical manifestations of the MPDs.

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