The Role of Inflammation and Inflammasome in Myeloproliferative Disease

Abstract

Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are rare hematological conditions known as myeloproliferative neoplasms (MPNs). They are characterized for being BCR-ABL negative malignancies and affected patients often present with symptoms which can significantly impact their quality of life. MPNs are characterized by a clonal proliferation of an abnormal hematopoietic stem/progenitor cell. In MPNs; cells of all myeloid lineages; including those involved in the immune and inflammatory response; may belong to the malignant clone thus leading to an altered immune response and an overexpression of cytokines and inflammatory receptors; further worsening chronic inflammation. Many of these cytokines; in particular, IL-1β and IL-18; are released in active form by activating the inflammasome complexes which in turn mediate the inflammatory process. Despite this; little is known about the functional effects of stem cell-driven inflammasome signaling in MPN pathogenesis. In this review we focused on the role of inflammatory pathway and inflammasome in MPN diseases. A better understanding of the inflammatory-state-driving MPNs and of the role of the inflammasome may provide new insights on possible therapeutic strategies

Genetics and Pathogenetic Role of Inflammasomes in Philadelphia Negative Chronic Myeloproliferative Neoplasms: A Narrative Review

“…Studies on the triggering of inflammatory processes in malignant hematopoiesis, with particular regard to MPNs, are focusing on the role of the innate immune system. The NLRP3 and AIM2 inflammasomes, which can recognize molecular patterns associated with pathogens and nuclear material of apoptotic cells, are mainly responsible for maintaining the cytokine storm, symptoms and end-organ damage that this group of diseases carry with them [ 49 , 50 ].…”

Inflammasomes and the Maintenance of Hematopoietic Homeostasis: New Perspectives and Opportunities

“…The inflammatory microenvironment of MPN is also related to the continuous release of proinflammatory cytokines, chemokines, and ROS in the hematopoietic stem cell compartment, which might lead to successive development of neoplasms [ 125 , 126 ]. MPNs include three main conditions: polycythemia vera, essential thrombocythemia, and myelofibrosis, which are related to frequent disease-related complications, including thrombosis, hemorrhage, and the transformation to MDS or AML [ 127 , 128 ]. It has been proven that inflammasome-associated chronic inflammation, as a hallmark of cancer development that affects all tumorigenesis stages, including initiation, promotion, malignant conversion, invasion, and metastasis, is driven by MPN neoplastic clones [ 129 , 130 ].…”

“…It has been proven that inflammasome-associated chronic inflammation, as a hallmark of cancer development that affects all tumorigenesis stages, including initiation, promotion, malignant conversion, invasion, and metastasis, is driven by MPN neoplastic clones [ 129 , 130 ]. In fact, cancer-related inflammation can be triggered by a series of signals from immune system cells including macrophages, neutrophils, T and B lymphocytes, and NK cells [ 128 ].…”

Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR–ABL-Negative Myeloproliferative Neoplasm

“…Pattern recognition receptor (PRR), an apoptosis-associated speck-like protein, and the cysteine protease caspase-1 are the general components of inflammasomes. Several different families belonging to PRRs have been described, including Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), Rig-I-like receptors (RLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), and C-type lectin receptors (CLRs) [21].…”