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Role of Inflammatory Factors during Disease Pathogenesis and Stem Cell Transplantation in Myeloproliferative Neoplasms
- Source :
- Cancers, Vol 12, Iss 2250, p 2250 (2020), Cancers
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Hematopoiesis is a highly regulated and complex process involving hematopoietic stem cells (HSCs), cell surface adhesion molecules, and cytokines as well as cells of the hematopoietic niche in the bone marrow (BM). Myeloproliferative neoplasms (MPNs) are characterized by clonal expansion of HSCs involving one or more blood cell lineages. Philadelphia-negative MPNs (Ph-neg MPNs) comprise polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In nearly all patients with Ph-neg MPN, mutations in the genes encoding janus kinase 2 (JAK2), calreticulin (CALR), or the thrombopoietin receptor (MPL) can be detected and, together with additional mutations in epigenetic modifier genes, these genetic aberrations contribute to the clonal expansion of the cells. In addition to these intracellular changes in the malignant clone, inflammatory processes involving both the clonal and the non-clonal cells contribute to the signs and symptoms of the patients, as well as to progression of the disease to myelofibrosis (MF) or acute leukemia, and to thrombotic complications. This contribution has been corroborated in preclinical studies including mouse models and patient-derived iPS cells, and in clinical trials, using anti-inflammatory drugs such as JAK inhibitors and steroids, or immunomodulatory drugs such as IMiDs and interferon-alpha (IFNa), all of which change the (im)balance of circulating inflammatory factors (e.g., TNFa, IL-1b, and TGFβ) in MPN. Currently, allogeneic hematopoietic (stem) cell transplantation (allo-HCT) remains the only curative treatment for Ph-neg MPN and is the treatment of choice in intermediate-2 and high-risk MF. HCT can reverse inflammatory changes induced by MPN as well as fibrosis in a large proportion of patients, but it also induces itself profound changes in inflammatory cells and cytokines in the patient, which may help to eradicate the disease but also in part cause significant morbidity (e.g., by graft-versus-host disease). In this review, we focus on the contribution of aberrant inflammation to disease pathogenesis in Ph-neg MPN as well as the current understanding of its alterations after allogeneic HCT.
- Subjects :
- 0301 basic medicine
Cancer Research
myeloproliferative neoplasm
Review
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
Polycythemia vera
medicine
allogeneic hematopoietic stem cell transplantation
Myelofibrosis
Myeloproliferative neoplasm
Thrombopoietin receptor
Janus kinase 2
JAK inhibitors
biology
business.industry
Essential thrombocythemia
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
cytokines
030104 developmental biology
medicine.anatomical_structure
Oncology
inflammation
030220 oncology & carcinogenesis
biology.protein
Cancer research
Bone marrow
Stem cell
business
Subjects
Details
- ISSN :
- 20726694
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....9e3c674f3df7875ad5ad186683b3a9e3