Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms
The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs) showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34+ cells of MPNs. Regarding lab...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/453020 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832549788394979328 |
|---|---|
| author | Vladan P. Čokić Olivera Mitrović-Ajtić Bojana B. Beleslin-Čokić Dragana Marković Marijana Buač Miloš Diklić Nada Kraguljac-Kurtović Svetozar Damjanović Pavle Milenković Mirjana Gotić Puri K. Raj |
| author_facet | Vladan P. Čokić Olivera Mitrović-Ajtić Bojana B. Beleslin-Čokić Dragana Marković Marijana Buač Miloš Diklić Nada Kraguljac-Kurtović Svetozar Damjanović Pavle Milenković Mirjana Gotić Puri K. Raj |
| author_sort | Vladan P. Čokić |
| collection | DOAJ |
| description | The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs) showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34+ cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV) and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF) patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET) and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34+ cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs. |
| format | Article |
| id | doaj-art-4875d06e34dc42e5aa02a133763630c9 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-4875d06e34dc42e5aa02a133763630c92025-02-03T06:08:32ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/453020453020Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative NeoplasmsVladan P. Čokić0Olivera Mitrović-Ajtić1Bojana B. Beleslin-Čokić2Dragana Marković3Marijana Buač4Miloš Diklić5Nada Kraguljac-Kurtović6Svetozar Damjanović7Pavle Milenković8Mirjana Gotić9Puri K. Raj10Institute for Medical Research, University of Belgrade, 11129 Belgrade, SerbiaInstitute for Medical Research, University of Belgrade, 11129 Belgrade, SerbiaClinic of Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, 11000 Belgrade, SerbiaInstitute for Medical Research, University of Belgrade, 11129 Belgrade, SerbiaInstitute for Medical Research, University of Belgrade, 11129 Belgrade, SerbiaInstitute for Medical Research, University of Belgrade, 11129 Belgrade, SerbiaClinic of Hematology, Clinical Center of Serbia, 11000 Belgrade, SerbiaClinic of Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, 11000 Belgrade, SerbiaInstitute for Medical Research, University of Belgrade, 11129 Belgrade, SerbiaClinic of Hematology, Clinical Center of Serbia, 11000 Belgrade, SerbiaDivision of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USAThe recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs) showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34+ cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV) and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF) patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET) and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34+ cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs.http://dx.doi.org/10.1155/2015/453020 |
| spellingShingle | Vladan P. Čokić Olivera Mitrović-Ajtić Bojana B. Beleslin-Čokić Dragana Marković Marijana Buač Miloš Diklić Nada Kraguljac-Kurtović Svetozar Damjanović Pavle Milenković Mirjana Gotić Puri K. Raj Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms Mediators of Inflammation |
| title | Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms |
| title_full | Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms |
| title_fullStr | Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms |
| title_full_unstemmed | Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms |
| title_short | Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms |
| title_sort | proinflammatory cytokine il 6 and jak stat signaling pathway in myeloproliferative neoplasms |
| url | http://dx.doi.org/10.1155/2015/453020 |
| work_keys_str_mv | AT vladanpcokic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT oliveramitrovicajtic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT bojanabbeleslincokic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT draganamarkovic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT marijanabuac proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT milosdiklic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT nadakraguljackurtovic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT svetozardamjanovic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT pavlemilenkovic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT mirjanagotic proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms AT purikraj proinflammatorycytokineil6andjakstatsignalingpathwayinmyeloproliferativeneoplasms |