The Role of NLRP3, a Star of Excellence in Myeloproliferative Neoplasms

Nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) is the most widely investigated inflammasome member whose overactivation can be a driver of several carcinomas. It is activated in response to different signals and plays an important role in metabolic disorders and inflammatory and autoimmune diseases. NLRP3 belongs to the pattern recognition receptors (PRRs) family, expressed in numerous immune cells, and it plays its primary function in myeloid cells. NLRP3 has a crucial role in myeloproliferative neoplasms (MPNs), considered to be the diseases best studied in the inflammasome context. The investigation of the NLRP3 inflammasome complex is a new horizon to explore, and inhibiting IL-1β or NLRP3 could be a helpful cancer-related therapeutic strategy to improve the existing protocols.

[1]  T. Reinheckel,et al.  Tyrosine kinase inhibitors can activate the NLRP3 inflammasome in myeloid cells through lysosomal damage and cell lysis , 2023, Science Signaling.

[2]  W. Vainchenker,et al.  Discovery of INCA033989, a Monoclonal Antibody That Selectively Antagonizes Mutant Calreticulin Oncogenic Function in Myeloproliferative Neoplasms (MPNs) , 2022, Blood.

[3]  T. Kanneganti,et al.  Humans pIKK-up NLRP3 to skip NEK7. , 2022, Trends in immunology.

[4]  Jonathan L. Schmid-Burgk,et al.  IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network. , 2022, Immunity.

[5]  J. Mascarenhas Pacritinib for the treatment of patients with myelofibrosis and thrombocytopenia , 2022, Expert review of hematology.

[6]  G. Basak,et al.  Inflammasomes—New Contributors to Blood Diseases , 2022, International journal of molecular sciences.

[7]  J. Wolchok,et al.  Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine , 2022, Science Translational Medicine.

[8]  Yong-Qing Wang,et al.  Imatinib-induced hepatotoxicity via oxidative stress and activation of NLRP3 inflammasome: an in vitro and in vivo study , 2022, Archives of Toxicology.

[9]  N. Bonadies,et al.  Inflammasome Activation in Myeloid Malignancies—Friend or Foe? , 2022, Frontiers in Cell and Developmental Biology.

[10]  Li Wang,et al.  The autoimmune encephalitis-related cytokine TSLP in the brain primes neuroinflammation by activating the JAK2-NLRP3 axis , 2021, Clinical and experimental immunology.

[11]  S. Aref,et al.  Predictive Value of miR-146a rs2431697 Polymorphism to Myelofibrosis Progression in Patients with Myeloproliferative Neoplasm , 2021, Asian Pacific journal of cancer prevention : APJCP.

[12]  A. Verma,et al.  Therapeutic targeting of the inflammasome in myeloid malignancies , 2021, Blood Cancer Journal.

[13]  X. Xiong,et al.  Janus Kinase Inhibition Ameliorates Ischemic Stroke Injury and Neuroinflammation Through Reducing NLRP3 Inflammasome Activation via JAK2/STAT3 Pathway Inhibition , 2021, Frontiers in Immunology.

[14]  A. Mackensen,et al.  β2-microglobulin triggers NLRP3 inflammasome activation in tumor-associated macrophages to promote multiple myeloma progression. , 2021, Immunity.

[15]  P. Pinton,et al.  Targeting the NLRP3 Inflammasome as a New Therapeutic Option for Overcoming Cancer , 2021, Cancers.

[16]  B. Fridley,et al.  Oxidized mitochondrial DNA released after inflammasome activation is a disease biomarker for myelodysplastic syndromes. , 2021, Blood advances.

[17]  T. Arora,et al.  NLRP3 inflammasome and bruton tyrosine kinase inhibition interferes with upregulated platelet aggregation and in vitro thrombus formation in sickle cell mice. , 2021, Biochemical and biophysical research communications.

[18]  A. Weber,et al.  Targeting the NLRP3 Inflammasome via BTK , 2021, Frontiers in Cell and Developmental Biology.

[19]  M. Napolitano,et al.  Genetics and Pathogenetic Role of Inflammasomes in Philadelphia Negative Chronic Myeloproliferative Neoplasms: A Narrative Review , 2021, International journal of molecular sciences.

[20]  D. Ma,et al.  NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway , 2020, Frontiers in Immunology.

[21]  J. Mascarenhas,et al.  Novel therapeutics in myeloproliferative neoplasms , 2020, Journal of Hematology & Oncology.

[22]  Jingxin Li,et al.  NLRP3 inflammasome upregulates PD-L1 expression and contributes to immune suppression in lymphoma. , 2020, Cancer letters.

[23]  S. Verstovsek,et al.  Novel Concepts of Treatment for Patients with Myelofibrosis and Related Neoplasms , 2020, Cancers.

[24]  D. Ma,et al.  Genetic polymorphisms and expression of NLRP3 inflammasome-related genes are associated with Philadelphia chromosome-negative myeloproliferative neoplasms. , 2020, Human immunology.

[25]  R. Zeiser,et al.  NLRP3 Inflammasome Activation in Cancer: A Double-Edged Sword , 2020, Frontiers in Immunology.

[26]  M. Ratajczak,et al.  The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis , 2020, Leukemia.

[27]  M. Konantz,et al.  Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation , 2020, Nature Communications.

[28]  T. Kanneganti,et al.  Toward targeting inflammasomes: insights into their regulation and activation , 2020, Cell Research.

[29]  Joo Young Lee,et al.  Direct Binding to NLRP3 Pyrin Domain as a Novel Strategy to Prevent NLRP3‐Driven Inflammation and Gouty Arthritis , 2020, Arthritis & rheumatology.

[30]  R. Skoda,et al.  IL-1β Secreted from Mutant Cells Carrying JAK2-V617Ffavors Early Clonal Expansion and Promotes MPN Disease Initiation and Progression , 2019, Blood.

[31]  Xi Wu,et al.  Pyroptosis: A new frontier in cancer. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[32]  D. Munn,et al.  Danger-associated extracellular ATP counters MDSC therapeutic efficacy in acute GvHD. , 2019, Blood.

[33]  N. Erez,et al.  NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis , 2019, Nature Communications.

[34]  Yuan He,et al.  The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation , 2019, International journal of molecular sciences.

[35]  C. Hamilton,et al.  Right place, right time: localisation and assembly of the NLRP3 inflammasome , 2019, F1000Research.

[36]  M. Ratajczak,et al.  The Nlrp3 Inflammasome Orchestrates Mobilization of Bone Marrow-Residing Stem Cells into Peripheral Blood , 2019, Stem Cell Reviews and Reports.

[37]  J. Ting,et al.  The NLRP3 inflammasome: molecular activation and regulation to therapeutics , 2019, Nature Reviews Immunology.

[38]  T. Kanneganti,et al.  Diverging inflammasome signals in tumorigenesis and potential targeting , 2019, Nature Reviews Cancer.

[39]  A. List,et al.  The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes. , 2019, Blood.

[40]  X. Zuo,et al.  Cytokines frequently implicated in myeloproliferative neoplasms , 2019, Cytokine: X.

[41]  E. Ejerblad,et al.  Inflammatory functional iron deficiency common in myelofibrosis, contributes to anaemia and impairs quality of life. From the Nordic MPN study Group , 2019, European journal of haematology.

[42]  Houhui Song,et al.  Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors , 2019, Cell Death & Disease.

[43]  Angela G. Fleischman,et al.  Defective negative regulation of Toll-like receptor signaling leads to excessive TNF-α in myeloproliferative neoplasm. , 2019, Blood advances.

[44]  S. Atkin,et al.  Role of the NLRP3 inflammasome in cancer , 2018, Molecular Cancer.

[45]  J. Nichols,et al.  The platelet NLRP3 inflammasome is upregulated in sickle cell disease via HMGB1/TLR4 and Bruton tyrosine kinase. , 2018, Blood advances.

[46]  D. Starczynowski,et al.  Chronic immune response dysregulation in MDS pathogenesis. , 2018, Blood.

[47]  B. Py,et al.  Spotlight on the NLRP3 inflammasome pathway , 2018, Journal of inflammation research.

[48]  Mingyi Zhao,et al.  NLRP3: A Novel Mediator in Cardiovascular Disease , 2018, Journal of immunology research.

[49]  J. Klco,et al.  TAK1 restricts spontaneous NLRP3 activation and cell death to control myeloid proliferation , 2018, The Journal of experimental medicine.

[50]  C. Stehlik,et al.  The oxidized phospholipid oxPAPC protects from septic shock by targeting the non-canonical inflammasome in macrophages , 2018, Nature Communications.

[51]  M. Ratajczak,et al.  Mobilization of hematopoietic stem cells as a result of innate immunity-mediated sterile inflammation in the bone marrow microenvironment—the involvement of extracellular nucleotides and purinergic signaling , 2018, Leukemia.

[52]  P. Brož,et al.  Function and mechanism of the pyrin inflammasome , 2018, European journal of immunology.

[53]  T. Kanneganti,et al.  Recent advances in inflammasome biology. , 2018, Current opinion in immunology.

[54]  D. Ma,et al.  The genetic polymorphism and expression profiles of NLRP3 inflammasome in patients with chronic myeloid leukemia. , 2018, Human immunology.

[55]  M. Previati,et al.  Mitochondria-associated membranes (MAMs) and inflammation , 2018, Cell Death & Disease.

[56]  F. Lussana,et al.  Inflammation and myeloproliferative neoplasms. , 2017, Journal of autoimmunity.

[57]  H. Nakanishi,et al.  NLRP3 mutation and cochlear autoinflammation cause syndromic and nonsyndromic hearing loss DFNA34 responsive to anakinra therapy , 2017, Proceedings of the National Academy of Sciences.

[58]  M. Netea,et al.  Targeting the interleukin-1 pathway in patients with hematological disorders. , 2017, Blood.

[59]  P. Frenette,et al.  Complexity of bone marrow hematopoietic stem cell niche , 2017, International Journal of Hematology.

[60]  W. Vainchenker,et al.  Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. , 2017, Blood.

[61]  A. Liston,et al.  Homeostasis-altering molecular processes as mechanisms of inflammasome activation , 2017, Nature Reviews Immunology.

[62]  A. Green,et al.  Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms , 2017, Haematologica.

[63]  G. Nolan,et al.  Mass Cytometry Analysis Reveals Hyperactive NF Kappa B Signaling in Myelofibrosis and Secondary Acute Myeloid Leukemia , 2016, Leukemia.

[64]  M. Ratajczak,et al.  Novel evidence that the mannan-binding lectin pathway of complement activation plays a pivotal role in triggering mobilization of hematopoietic stem/progenitor cells by activation of both the complement and coagulation cascades , 2016, Leukemia.

[65]  J. Cleveland,et al.  The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype. , 2016, Blood.

[66]  A. Tefferi,et al.  Targeted deep sequencing in primary myelofibrosis. , 2016, Blood advances.

[67]  I. Hitchcock,et al.  Endothelial JAK2V617F Expression Drives Inflammation and Cellular Senescence; New Evidence for the Roles of Endothelial Cells in MPN-Related Clotting Abnormalities? , 2016 .

[68]  G. Rivas,et al.  ASC Pyrin Domain Self-associates and Binds NLRP3 Protein Using Equivalent Binding Interfaces * , 2016, The Journal of Biological Chemistry.

[69]  J. Rathmell,et al.  A guide to immunometabolism for immunologists , 2016, Nature Reviews Immunology.

[70]  V. Dixit,et al.  Inflammasomes: mechanism of assembly, regulation and signalling , 2016, Nature Reviews Immunology.

[71]  C. Kemper,et al.  A novel “complement–metabolism–inflammasome axis” as a key regulator of immune cell effector function , 2016, European journal of immunology.

[72]  Jonathan L. Schmid-Burgk,et al.  Human Monocytes Engage an Alternative Inflammasome Pathway. , 2016, Immunity.

[73]  T. Barbui,et al.  Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both , 2016, Leukemia.

[74]  Kolsoum Saeidi Myeloproliferative neoplasms: Current molecular biology and genetics. , 2016, Critical reviews in oncology/hematology.

[75]  G. Núñez,et al.  Nek7 is an essential mediator of NLRP3 activation downstream of potassium efflux , 2016, Nature.

[76]  C. Sasakawa,et al.  Molecular mechanisms regulating NLRP3 inflammasome activation , 2015, Cellular and Molecular Immunology.

[77]  D. Su,et al.  NLRP3 inflammasome and its inhibitors: a review , 2015, Front. Pharmacol..

[78]  H. Hasselbalch,et al.  MPNs as Inflammatory Diseases: The Evidence, Consequences, and Perspectives , 2015, Mediators of inflammation.

[79]  A. Dueck,et al.  Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development , 2015, Mediators of inflammation.

[80]  Jonathan L. Schmid-Burgk,et al.  Caspase‐4 mediates non‐canonical activation of the NLRP3 inflammasome in human myeloid cells , 2015, European journal of immunology.

[81]  S. Kummerfeld,et al.  Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling , 2015, Nature.

[82]  S. Ryter,et al.  mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation. , 2015, Cell reports.

[83]  R. Morita,et al.  Bruton's tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury , 2015, Nature Communications.

[84]  J. Apperley Chronic myeloid leukaemia , 2015, The Lancet.

[85]  Ayalew Tefferi,et al.  Myeloproliferative Neoplasms A Contemporary Review , 2015 .

[86]  S. Colla,et al.  Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes , 2015, Leukemia.

[87]  K. Schroder,et al.  A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases , 2015, Nature Medicine.

[88]  Jonathan J. Chen,et al.  JAK-STAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic response. , 2015, Cancer discovery.

[89]  Hong Wang,et al.  Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction- a novel mechanism for maintaining vascular function , 2014, Journal of Hematology & Oncology.

[90]  A. V. Villamil Giraldo,et al.  Lysosomotropic agents: impact on lysosomal membrane permeabilization and cell death. , 2014, Biochemical Society transactions.

[91]  D. Lai,et al.  Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms , 2014, Nature.

[92]  Dan Fu,et al.  Imaging the Intracellular Distribution of Tyrosine Kinase Inhibitors in Living Cells with Quantitative Hyperspectral Stimulated Raman Scattering , 2014, Nature chemistry.

[93]  A. Green,et al.  CALR mutations in myeloproliferative neoplasms: Hidden behind the reticulum , 2014, American journal of hematology.

[94]  Christian Beisel,et al.  Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. , 2014, Blood.

[95]  F. Passamonti,et al.  CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons , 2014, Leukemia.

[96]  G. Superti-Furga,et al.  Somatic mutations of calreticulin in myeloproliferative neoplasms. , 2013, The New England journal of medicine.

[97]  James L. Mueller,et al.  Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies. , 2013, The Journal of clinical investigation.

[98]  C. Wijekoon,et al.  Biochemical and structural aspects of the ATP‐binding domain in inflammasome‐forming human NLRP proteins , 2013, IUBMB life.

[99]  G. Núñez,et al.  K⁺ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. , 2013, Immunity.

[100]  E. Latz,et al.  Activation and regulation of the inflammasomes , 2013, Nature Reviews Immunology.

[101]  H. Hasselbalch Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development? , 2013, Leukemia research.

[102]  Richard A. Flavell,et al.  Inflammasomes in health and disease , 2012, Nature.

[103]  P. Linsley,et al.  miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice , 2011, The Journal of experimental medicine.

[104]  Grace Y Chen,et al.  Sterile inflammation: sensing and reacting to damage , 2010, Nature Reviews Immunology.

[105]  M. Rocchi,et al.  Non random distribution of genomic features in breakpoint regions involved in chronic myeloid leukemia cases with variant t(9;22) or additional chromosomal rearrangements , 2010, Molecular Cancer.

[106]  M. Rocchi,et al.  Genomic segmental duplications on the basis of the t(9;22) rearrangement in chronic myeloid leukemia , 2010, Oncogene.

[107]  S. Akira,et al.  Pattern Recognition Receptors and Inflammation , 2010, Cell.

[108]  J. Tschopp,et al.  The Inflammasomes , 2010, Cell.

[109]  R. Koch,et al.  ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drug , 2009, Haematologica.

[110]  J. Tschopp,et al.  Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors , 2009, Nature Medicine.

[111]  C. Bloomfield,et al.  The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. , 2009, Blood.

[112]  L. Joosten,et al.  Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. , 2009, Blood.

[113]  B. Cookson,et al.  Pyroptosis: host cell death and inflammation , 2009, Nature Reviews Microbiology.

[114]  P. Allavena,et al.  Cancer-related inflammation , 2008, Nature.

[115]  PhD Cuihua Zhang MD The role of inflammatory cytokines in endothelial dysfunction , 2008, Basic Research in Cardiology.

[116]  David A. Williams,et al.  TNF-α induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells , 2007 .

[117]  M. Minden,et al.  Myelodysplastic syndromes: the complexity of stem-cell diseases , 2007, Nature Reviews Cancer.

[118]  D. Baltimore,et al.  NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses , 2006, Proceedings of the National Academy of Sciences.

[119]  A. Weinberg,et al.  IL-18 Bridges Innate and Adaptive Immunity through IFN-γ and the CD134 Pathway1 , 2006, The Journal of Immunology.

[120]  Alan Aderem,et al.  Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf , 2006, Nature Immunology.

[121]  Mario Cazzola,et al.  A gain-of-function mutation of JAK2 in myeloproliferative disorders. , 2005, The New England journal of medicine.

[122]  Sandra A. Moore,et al.  Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. , 2005, Cancer cell.

[123]  P. Campbell,et al.  Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders , 2005, The Lancet.

[124]  Luigi Ferrucci,et al.  Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. , 2004, Blood.

[125]  G. Fantuzzi,et al.  Interleukin-18 and Interleukin-1β: Two Cytokine Substrates for ICE (Caspase-1) , 2004, Journal of Clinical Immunology.

[126]  H. Kantarjian,et al.  Acute myeloid leukemia , 2018, Methods in Molecular Biology.

[127]  W. Jelkmann,et al.  Proinflammatory cytokines lowering erythropoietin production. , 1998, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.