dc.creator | Diklić, M. | |
dc.creator | Marković, D. | |
dc.creator | Đikić, D. | |
dc.creator | Milanović, Svetlana | |
dc.creator | Mojsilović, Slavko | |
dc.creator | Jovčić, Gordana | |
dc.creator | Cokić, V. P. | |
dc.date.accessioned | 2020-06-03T13:47:32Z | |
dc.date.available | 2020-06-03T13:47:32Z | |
dc.date.issued | 2014 | |
dc.identifier.issn | 0390-6078 | |
dc.identifier.uri | https://vet-erinar.vet.bg.ac.rs/handle/123456789/1087 | |
dc.description.abstract | Background: Oxidative stress is an invasive condition with increased reactive
oxygen species, now recognized as an important characteristic of malignant
disorders as well as their progression.
Aims: The aim of this study was to evaluate the role of oxidative stress induced
genes and antioxidative enzymes in myeloproliferative neoplasms (MPN):
polycythemia vera (PV), essential thrombocythemia (ET) and primary
myelofibrosis (PMF).
Methods: Using microarray analysis we studied oxidative stress induced gene
expression in CD34+ hematopoietic progenitors of MPN patients. An assay for
superoxide dismutases (SOD) was based on the ability of SOD to inhibit the
autoxidation of epinephrine at alkaline pH. The activity of glutathione reductase
(GR) was based on the capacity of GR to catalyze the reduction of oxidized to
reduced glutathione using NADPH as a substrate. Glutathione peroxidase
activity was assayed following the oxidation of NADPH with t-butylhydroperoxide as a substrate. The antioxidative enzymes activities were
determined in red blood cells lyzate.
Results: Oxidative stress induced FBJ murine osteosarcoma viral oncogene
homolog (FOS) gene expression was highly elevated in ET (3.1 fold) and PV (3.7
fold) comparing to healthy controls. FOS gene expression was higher in
JAK2V617F heterozygous PV patients (4.1 fold). Less prominent expression
was observed for kelch-like ECH-associated protein 1 (KEAP1) gene in PV (1.6
fold) and PMF (1.8 fold). Regarding ET patients, heme oxygenase 1 (HMOX1)
gene was preferentially expressed in JAK2V617F positive ET (2.4 fold),
significantly higher than in healthy controls (p<0.05). Also, HMOX1 was
significantly more expressed in JAK2V617F homozygous PV patients (2.5 fold),
than in healthy controls (p<0.05). In contrary, v-maf musculoaponeurotic
fibrosarcoma oncogene homolog F (MAFF) gene was significantly less expressed
in JAK2 homozygous PV and PMF than in healthy controls (p<0.01). The levels
of superoxide dismutase and glutathione peroxidase were the most abundant in
PMF of MPN. The level of glutathione reductase was the highest in PV, not
influenced by JAK2V617F mutant allele burden. However in PMF, the level of
glutathione reductase was the most increased in JAK2 homozygous PMF and
reduced in JAK2 negative patients, in opposite to glutathione peroxidase levels.
Summary and Conclusions: Presented oxidative stress induced gene
expression demonstrated JAK2 dependence in MPN. The antioxidative enzymes
activities were the most prominent in PMF. So, oxidative stress effects both at
gene and enzyme levels revealed a variation specific for certain type of MPN. | |
dc.publisher | Ferrata Storti Foundation, Pavia | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Haematologica | |
dc.title | Oxidative stress in myeloproliferative neoplasms | en |
dc.type | conferenceObject | |
dc.rights.license | BY | |
dcterms.abstract | Милановић, Светлана; Ђикић, Д.; Марковић, Д.; Цокић, В. П.; Диклић, М.; Мојсиловић, Славко; Јовчић, Гордана; | |
dc.citation.volume | 99 | |
dc.citation.spage | 662 | |
dc.citation.epage | 662 | |
dc.citation.other | 99: 662-662 | |
dc.citation.rank | aM21 | |
dc.identifier.wos | 000342830903207 | |
dc.identifier.fulltext | http://veterinar.vet.bg.ac.rs/bitstream/id/7085/bitstream_7085.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_veterinar_1087 | |
dc.type.version | publishedVersion | |