Chronic Inflammation in Primary Myelofibrosis: In-Depth Insights Into Pathogenesis and Promising Anti-Inflammatory Therapeutic Strategies

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm (MPN) stemming from hematopoietic stem and progenitor cells (HSPCs), frequently associated with mutations in Janus kinase signal transducer (JAK2), calreticulin (CALR), or thrombopoietin receptor (MPL). Characterized by intricate clonality and dysregulated inflammation, PMF leads to heightened morbidity, mortality, and an elevated risk of leukemic transformation. The inflammatory state in PMF results from the convoluted interplay of excessive inflammatory mediator production, heightened oxidative stress, and immune system dysregulation. These factors fuel the expansion of the myeloproliferative clone, accelerate disease progression toward leukemia, and contribute to bone marrow (BM) fibrosis by acting on BM stromal cells. This review comprehensively integrates recent research findings, especially those from single‐cell RNA sequencing, to identify the sources and regulatory mechanisms of inflammatory mediator overproduction, oxidative stress, and immune system dysregulation in PMF. It also elaborates on the key cytokines and pathways governing the interaction between malignant hematopoietic cells and BM stromal cells. By providing a comprehensive perspective, this review aims to guide future research on cellular and molecular targets within the hematopoietic niche and explore therapeutic approaches targeting immune cells and cytokines for PMF treatment. The potential of anti‐inflammatory therapies in the clinical management of PMF is also highlighted.

• Publication year

  2025

• Venue

  Mediators of Inflammation

• Publication date

  2025-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1155/mi/9967975PMID 41268532PMCID 12629696
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Oncogenic Calreticulin Induces Immune Escape by Stimulating TGF-β Expression and Regulatory T Cell Expansion in the Bone Marrow Microenvironment

  2024cited by this paper
• Proteomic screening identifies PF4/Cxcl4 as a critical driver of myelofibrosis

  2024cited by this paper
• miR‐146a−/− mice model reveals that NF‐κB inhibition reverts inflammation‐driven myelofibrosis‐like phenotype

  2024cited by this paper
• Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitor INCB057643 in Patients with Relapsed or Refractory Myelofibrosis and Other Advanced Myeloid Neoplasms: A Phase 1 Study

  2024cited by this paper
• Proinflammatory phenotype of iPS cell-derived JAK2 V617F megakaryocytes induces fibrosis in 3D in vitro bone marrow niche

  2024cited by this paper
• A Phase Ib, Open-Label Study of Add on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib

  2024cited by this paper
• Different inflammatory, fibrotic, and immunological signatures between pre-fibrotic and overt primary myelofibrosis

  2024cited by this paper
• Neutrophil extracellular traps in homeostasis and disease

  2024cited by this paper
• Targeting cytokine and chemokine signaling pathways for cancer therapy

  2024cited by this paper
• Elevated levels of damage-associated molecular patterns HMGB1 and S100A8/A9 coupled with toll-like receptor-triggered monocyte activation are associated with inflammation in patients with myelofibrosis

  2024cited by this paper
• IDH2 mutation accelerates TPO‐induced myelofibrosis with enhanced S100a8/a9 and NFκB signaling in vivo

  2024cited by this paper
• Immunophenotype of myeloid granulocytes in Chinese patients with BCR::ABL1-negative myeloproliferative neoplasms

  2024cited by this paper
• Clonal hematopoiesis and hematological malignancy

  2024cited by this paper
• Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis

  2024cited by this paper
• Targeting exhausted cytotoxic T cells through CTLA‐4 inhibition promotes elimination of neoplastic cells in human myelofibrosis xenografts

  2024cited by this paper
• Inflammasome components as new therapeutic targets in inflammatory disease

  2024cited by this paper
• Selective targeting of mutated calreticulin by the monoclonal antibody INCA033989 inhibits oncogenic function of MPN.

  2024cited by this paper
• Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia

  2024cited by this paper
• Circulating Polymorphonuclear Myeloid-Derived Suppressor Cells (PMN-MDSCs) Have a Biological Role in Patients with Primary Myelofibrosis

  2024cited by this paper
• CD38 Overexpressed Monocytes Play a Critical Role in the Fibrogenesis in Myeloproliferative Neoplasms and Can be Used As a Therapeutic Target to Ameliorate Fibrosis

  2024cited by this paper
• Deregulation of the p19/CDK4/CDK6 axis in Jak2V617F megakaryocytes accelerates the development of myelofibrosis

  2024cited by this paper
• Exacerbation of thromboinflammation by JAK2V617F mutation worsens the prognosis of cerebral venous sinus thrombosis

  2024cited by this paper
• Endothelial LATS2 is a suppressor of bone marrow fibrosis

  2024cited by this paper
• Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC-Alarmin Axis.

  2024cited by this paper
• The clonal hematopoiesis mutation Jak2V617F aggravates endothelial injury and thrombosis in arteries with erosion-like intimas.

  2024cited by this paper
• The IL-1β inhibitor canakinumab in previously treated lower-risk myelodysplastic syndromes: a phase 2 clinical trial

  2024cited by this paper
• IL-1β promotes MPN disease initiation by favoring early clonal expansion of JAK2-mutant hematopoietic stem cells

  2024cited by this paper
• Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

  2023cited by this paper
• Immunosenescence: molecular mechanisms and diseases

  2023cited by this paper
• A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases.

  2023cited by this paper
• A pro-inflammatory stem cell niche drives myelofibrosis through a targetable galectin-1 axis

  2023influential reference
• Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution

  2023cited by this paper
• Primary myelofibrosis: 2023 update on diagnosis, risk‐stratification, and management

  2023cited by this paper
• Systematic dissection of coordinated stromal remodeling identifies Sox10+ glial cells as a therapeutic target in myelofibrosis.

  2023cited by this paper
• Platelets and neutrophils cooperate to induce increased NETosis in JAK2V617F myeloproliferative neoplasms.

  2023cited by this paper
• Dupilumab in Inflammatory Skin Diseases: A Systematic Review

  2023cited by this paper
• In vivo ablation of NFκB cascade effectors alleviates disease burden in myeloproliferative neoplasms.

  2023cited by this paper
• Inhibition of CXCR1/2 reduces the emperipolesis between neutrophils and megakaryocytes in the Gata1low model of myelofibrosis

  2023cited by this paper
• Discovery of JNJ-88549968, a Novel, First-in-Class CALRmutxCD3 T-Cell Redirecting Antibody for the Treatment of Myeloproliferative Neoplasms

  2023cited by this paper
• MANIFEST: Pelabresib in Combination With Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Myelofibrosis

  2023cited by this paper
• Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial

  2023cited by this paper
• Micheliolide exerts effects in myeloproliferative neoplasms through inhibiting STAT3/5 phosphorylation via covalent binding to STAT3/5 proteins

  2023cited by this paper
• Characterizing the microbiome of patients with myeloproliferative neoplasms during a Mediterranean diet intervention

  2023cited by this paper
• Characterizing the microbiome of patients with myeloproliferative neoplasms during a Mediterranean diet intervention

  2023cited by this paper
• Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

  2023cited by this paper
• S100A8 and S100A9 in Cancer.

  2023cited by this paper
• Mutation-Driven S100A8 Overexpression Confers Aberrant Phenotypes in Type 1 CALR-Mutated MPN

  2023cited by this paper
• Newly identified roles for PIEZO1 mechanosensor in controlling normal megakaryocyte development and in primary myelofibrosis

  2023cited by this paper
• The roles of inflammasomes in cancer

  2023cited by this paper
• A Phase Ib, Open-Label Study of Add on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib

  2023cited by this paper
• SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm

  2023cited by this paper
• Phase 1 Results of the First-in-Class CXCR1/2 Inhibitor SX-682 in Patients with Hypomethylating Agent Failure Myelodysplastic Syndromes

  2022cited by this paper
• In utero origin of myelofibrosis presenting in adult monozygotic twins

  2022cited by this paper
• Hallmarks of aging: An expanding universe.

  2022cited by this paper
• The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

  2022cited by this paper
• Single-cell analysis of acute lymphoblastic and lineage ambiguous leukemia - approaches and molecular insights.

  2022cited by this paper
• Philadelphia-negative myeloproliferative neoplasms display alterations in monocyte subpopulations frequency and immunophenotype

  2022cited by this paper
• IL-13/IL-4 signaling contributes to fibrotic progression of the myeloproliferative neoplasms.

  2022cited by this paper
• OUP accepted manuscript

  2022cited by this paper
• The CXCR1/CXCR2 Inhibitor Reparixin Alters the Development of Myelofibrosis in the Gata1 low Mice

  2022cited by this paper
• Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm

  2022cited by this paper
• PD‐L1 overexpression correlates with JAK2‐V617F mutational burden and is associated with 9p uniparental disomy in myeloproliferative neoplasms

  2022cited by this paper
• Therapeutic activity of GARP:TGF-β1 blockade in murine primary myelofibrosis

  2022cited by this paper
• Life histories of myeloproliferative neoplasms inferred from phylogenies

  2022cited by this paper
• The Response to Oxidative Damage Correlates with Driver Mutations and Clinical Outcome in Patients with Myelofibrosis

  2022cited by this paper
• Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)

  2022cited by this paper
• TGF-β signaling in myeloproliferative neoplasms contributes to myelofibrosis without disrupting the hematopoietic niche

  2022influential reference
• ASXL1 mutations accelerate bone marrow fibrosis via EGR1-TNFA axis-mediated neoplastic fibrocyte generation in myeloproliferative neoplasms

  2022influential reference
• Genetic basis and molecular profiling in myeloproliferative neoplasms

  2022cited by this paper
• Anti-inflammatory treatment in MPN: targeting TNFR1 and TNFR2 in JAK2-V617F–induced disease

  2021cited by this paper
• The immune landscape in BCR‐ABL negative myeloproliferative neoplasms: inflammation, infections and opportunities for immunotherapy

  2021cited by this paper
• The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis

  2021cited by this paper
• Histone deacetylase inhibitors for cardiovascular conditions and healthy longevity.

  2021cited by this paper
• G6b-B regulates an essential step in megakaryocyte maturation

  2021cited by this paper
• The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

  2021cited by this paper
• Molecular pathogenesis of the myeloproliferative neoplasms

  2021cited by this paper
• NK Cells in Myeloproliferative Neoplasms (MPN)

  2021cited by this paper
• Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity

  2021cited by this paper
• CXCL8 Signaling in the Tumor Microenvironment.

  2021cited by this paper
• Clonal dynamics of haematopoiesis across the human lifespan

  2021cited by this paper
• CXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis

  2021influential reference
• The Interleukin‐1 Receptor–Associated Kinase 4 Inhibitor PF‐06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial

  2021cited by this paper
• The use of luspatercept for thalassemia in adults.

  2021cited by this paper
• The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies

  2021cited by this paper
• JAK2V617F mutant megakaryocytes contribute to hematopoietic aging in a murine model of myeloproliferative neoplasm

  2021cited by this paper
• Next Generation Therapeutics for the Treatment of Myelofibrosis

  2021cited by this paper
• A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis

  2021cited by this paper
• Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy.

  2021cited by this paper
• Identification of CXCL12‐abundant reticular cells in human adult bone marrow

  2021cited by this paper
• Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR–ABL-Negative Myeloproliferative Neoplasm

  2020cited by this paper
• Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets

  2020cited by this paper
• Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns.

  2020cited by this paper
• Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis

  2020influential reference
• The role of circulating monocytes and JAK inhibition in the infectious-driven inflammatory response of myelofibrosis

  2020cited by this paper
• Ker-050, a Novel Inhibitor of Tgfβ Superfamily Signaling, Induces Red Blood Cell Production By Promoting Multiple Stages of Erythroid Differentiation

  2020cited by this paper
• Cytokine Profiling as a Novel Complementary Tool to Predict Prognosis in MPNs?

  2020cited by this paper
• Neoplastic fibrocytes play an essential role in bone marrow fibrosis in Jak2V617F-induced primary myelofibrosis mice

  2020cited by this paper
• Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

  2020cited by this paper
• Iron regulates myeloma cell/macrophage interaction and drives resistance to bortezomib

  2020cited by this paper
• Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN.

  2020cited by this paper

• No citing papers are available for this paper.