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Role of inflammation in the biology of myeloproliferative neoplasms.
Metadata
Journalblood reviews5.823Date
2020 May 30
4 months ago
Type
Research Support, Non-U.S. Gov't
Review
Journal Article
Volume
2020-07 / 42 : 100711
Author
Koschmieder S 1, Chatain N 2
Affiliation
  • 2. Department of Hematology, Oncology, Hemostaselogy, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany. Electronic address: [email protected]
Doi
PMIDMESH
Abstract
What is the role of inflammation in Myeloproliferative Neoplasms? This is currently a topic of much debate. In this review, we will discuss experimental results and basic concepts of inflammatory processes in the pathogenesis of myeloproliferative neoplasms (MPN). So, which are the players involved? First, these are the clonal hematopoietic stem cells (HSC) and their normal stem cell counterparts in the bone marrow (BM), as well as their more mature progeny in the BM and the peripheral blood (PB), including neutrophils, macrophages, erythrocytes, and platelets, but also other cell lineages. Second, these cells produce a plethora of inflammatory cytokines, such as interleukin 6 (IL6), interleukin 8 (IL8), TNF-alpha (TNFa), interferon-alpha (IFNa), and others. Third, these cells and cytokines act in concert with non-hematopoietic cells, including endothelial cells and mesenchymal stromal cells (MSCs). The latter cells, in particular GLI1 positive or leptin receptor (LepR) positive stromal cells, may become activated by the hematopoietic clone to give rise to myofibroblasts, producing excessive fibrosis in the bone marrow (myelofibrosis). Ultimately, the inflammatory and fibrotic circuit involving these three key players may lead to progression of the disease, resulting in BM failure and transformation into acute leukemia, also termed blast crisis. Here, we review the role of these three effectors in the pathogenesis of MPN.
Keywords: Clonal hematopoietic cells Inflammation Interferon Microenvironment Myeloproliferative neoplasms (MPN) Myofibroblasts Stromal cells Transcriptomics
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5.8
Blood Revblood reviews
Metadata
LocationEngland
FromCHURCHILL LIVINGSTONE

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