Research

Gene and microRNA analysis of neutrophils from patients with polycythemia vera and essential thrombocytosis: down-regulation of micro RNA-1 and -133a

Stefanie Slezak¹ , Ping Jin¹ , Lorraine Caruccio¹ , Jiaqiang Ren¹ , Michael Bennett² , Nausheen Zia¹ , Sharon Adams¹ , Ena Wang¹ , Joao Ascensao³ , Geraldine Schechter³ and David Stroncek¹

¹  Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

²  Department of Hematology, Emek Hospital, Afula, Israel

³  Hematology Section, Veterans Affairs Medical Center, Washington DC, USA

author email corresponding author email

Journal of Translational Medicine 2009, 7:39doi:10.1186/1479-5876-7-39

Published:	4 June 2009

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.