pSTAT5 and ERK exhibit different expression in myeloproliferative neoplasms

Wiśniewska-Chudy,Ewa; Szylberg,Łukasz; Dworacki,Grzegorz; Mizera-Nyczak,Ewa; Marszałek,Andrzej

doi:10.3892/or.2017.5476

pSTAT5 and ERK exhibit different expression in myeloproliferative neoplasms

Authors:
- Ewa Wiśniewska-Chudy
- Łukasz Szylberg
- Grzegorz Dworacki
- Ewa Mizera-Nyczak
- Andrzej Marszałek
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Affiliations: Department of Clinical Pathomorphology, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85-092 Bydgoszcz, Poland, Department of Clinical Immunology, Poznań University of Medical Sciences, 60-806 Poznań, Poland, Department of Oncology, Greater Poland Cancer Centre, 61-866 Poznań, Poland
Published online on: February 24, 2017 https://doi.org/10.3892/or.2017.5476
Pages: 2295-2307

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Abstract

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic progenitor cell disorders characterized by the proliferation of one or more hematopoietic lineages. The classical MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) entities. These disorders are characterized by bone marrow morphology typical for each disease, and by the presence of JAK2V617F mutation in the marrow and blood. However, JAK2V617F cannot account for the phenotypic heterogeneity of MPNs because approximately half of all cases of ET and PMF show no evidence of this molecular marker. Therefore, the search for novel markers of these diseases is necessary to improve pathomorphological and molecular diagnostics. This study aimed to investigate the changes in expression patterns of the proteins STAT5 (the signal transducers and activators of transcription 5) and ERK (extracellular signal-regulated kinase) in bone marrow trephine specimens, derived both from patients with wild-type and mutant (V617F) forms of JAK2 kinase. Furthermore, the changes in STAT5 and ERK2 gene expression levels in the same patients were also investigated. The results of our immunohistochemical, immunoblotting and RT-qPCR studies revealed at least four major unique features of three types of MPNs. These include: i) more pronounced expression of phosphoSTAT5 protein in patients with JAK2V617F mutation compared to patients with wild-type of JAK2 kinase ii) different expression pattern of pSTAT5 in the nucleus and the cytoplasm of megakaryocytes and other bone marrow cells; iii) approximately 5-fold higher expression level of STAT5a gene in PV in comparison to patients with PMF and approximately 2-fold higher than in ET patients; iv) different, intracellular expression patterns of ERK2 and ERK1/2 antigens allowed to distinguish each subtype of MPN. These abnormalities in expression patterns of STAT5 and ERK proteins and genes provide some novel molecular features of MPNs and brings us closer to explaining the pathogenesis of MPNs.

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