Remodeling the Bone Marrow Microenvironment - A Proposal for Targeting Pro-inflammatory Contributors in MPN
- PMID: 32983162
- PMCID: PMC7489333
- DOI: 10.3389/fimmu.2020.02093
Remodeling the Bone Marrow Microenvironment - A Proposal for Targeting Pro-inflammatory Contributors in MPN
Abstract
Philadelphia-negative myeloproliferative neoplasms (MPN) are malignant bone marrow (BM) disorders, typically arising from a single somatically mutated hematopoietic stem cell. The most commonly mutated genes, JAK2, CALR, and MPL lead to constitutively active JAK-STAT signaling. Common clinical features include myeloproliferation, splenomegaly and constitutional symptoms. This review covers the contributions of cellular components of MPN pathology (e.g., monocytes, megakaryocytes, and mesenchymal stromal cells) as well as cytokines and soluble mediators to the development of myelofibrosis (MF) and highlights recent therapeutic advances. These findings outline the importance of malignant and non-malignant BM constituents to the pathogenesis and treatment of MF.
Keywords: CALR; JAK2; MPL; MPN; inflammation; megakaryocytes; mesenchymal stromal cells; monocytes.
Copyright © 2020 Jutzi and Mullally.
Similar articles
-
Changing concepts of diagnostic criteria of myeloproliferative disorders and the molecular etiology and classification of myeloproliferative neoplasms: from Dameshek 1950 to Vainchenker 2005 and beyond.Acta Haematol. 2015;133(1):36-51. doi: 10.1159/000358580. Epub 2014 Aug 7. Acta Haematol. 2015. PMID: 25116092 Review.
-
Pathogenesis of myeloproliferative neoplasms.Exp Hematol. 2015 Aug;43(8):599-608. doi: 10.1016/j.exphem.2015.06.007. Epub 2015 Jul 21. Exp Hematol. 2015. PMID: 26209551 Review.
-
Mechanism underlying the development of myeloproliferative neoplasms through mutant calreticulin.Cancer Sci. 2020 Aug;111(8):2682-2688. doi: 10.1111/cas.14503. Epub 2020 Jun 27. Cancer Sci. 2020. PMID: 32462673 Free PMC article. Review.
-
The Role of Neutrophilic Granulocytes in Philadelphia Chromosome Negative Myeloproliferative Neoplasms.Int J Mol Sci. 2021 Sep 3;22(17):9555. doi: 10.3390/ijms22179555. Int J Mol Sci. 2021. PMID: 34502471 Free PMC article. Review.
-
Activation of JAK/STAT Signaling in Megakaryocytes Sustains Myeloproliferation In Vivo.Clin Cancer Res. 2019 Oct 1;25(19):5901-5912. doi: 10.1158/1078-0432.CCR-18-4089. Epub 2019 Jun 19. Clin Cancer Res. 2019. PMID: 31217200 Free PMC article.
Cited by
-
High cell-free DNA is associated with disease progression, inflammasome activation and elevated levels of inflammasome-related cytokine IL-18 in patients with myelofibrosis.Front Immunol. 2023 Nov 16;14:1161832. doi: 10.3389/fimmu.2023.1161832. eCollection 2023. Front Immunol. 2023. PMID: 38035089 Free PMC article.
-
Impact of the rs1024611 Polymorphism of CCL2 on the Pathophysiology and Outcome of Primary Myelofibrosis.Cancers (Basel). 2021 May 22;13(11):2552. doi: 10.3390/cancers13112552. Cancers (Basel). 2021. PMID: 34067466 Free PMC article.
-
USP5 inhibition via bone marrow-targeted engineered exosomes for myeloproliferative neoplasms therapy.J Nanobiotechnology. 2025 Jul 11;23(1):501. doi: 10.1186/s12951-025-03588-4. J Nanobiotechnology. 2025. PMID: 40646529 Free PMC article.
-
Oncogenic Calreticulin Induces Immune Escape by Stimulating TGFβ Expression and Regulatory T-cell Expansion in the Bone Marrow Microenvironment.Cancer Res. 2024 Sep 16;84(18):2985-3003. doi: 10.1158/0008-5472.CAN-23-3553. Cancer Res. 2024. PMID: 38885318 Free PMC article.
-
Anti-IL-6 cytokine treatment has no impact on elevated hematocrit or splenomegaly in a polycythemia vera mouse model.Blood Adv. 2022 Jan 25;6(2):399-404. doi: 10.1182/bloodadvances.2021004379. Blood Adv. 2022. PMID: 34559181 Free PMC article.
References
-
- Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. (2020) 7:e196–208. 10.1016/s2352-3026(19)30236-4 - DOI - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous