Abstract
PURPOSE OF REVIEW: Thrombosis remains a leading cause of morbidity and mortality in BCR/ABL negative myeloproliferative neoplasms (MPN). Circulating blood cells are both increased in quantity and qualitatively abnormal in MPN, resulting in an increased thrombotic risk. Herein, we review recently elucidated mechanisms of MPN thrombosis and discuss implications of drugs currently under investigation for MPN.
RECENT FINDINGS: Recent studies highlight that in JAK2 V617F granulocytes and platelets, thrombo-inflammatory genes are upregulated. Furthermore, in JAK2 V617F granulocytes, protein expression of integrin CD11b, tissue factor, and leukocyte alkaline phosphatase are all increased. Overall, myeloid cells, namely neutrophils, may contribute in several ways, such as through increased adhesion via β1 integrin binding to VCAM1, increased infiltration, and enhanced inducibility to extrude neutrophil extracellular traps. Non-myeloid inflammatory cells may also contribute via secretion of cytokines. With regard to red blood cells, number, rigidity, adhesion, and generation of microvesicles may lead to increased vascular resistance as well as increased cell-cell interactions that promote rolling and adhesion. Platelets may also contribute in a similar fashion. Lastly, the vasculature is also increasingly appreciated, as several studies have demonstrated increased endothelial expression of pro-coagulant and pro-adhesive proteins, such as von Willebrand factor or P-selectin in JAK2 V617F endothelial cells. With the advent of molecular diagnostics, MPN therapeutics are advancing beyond cytoreduction. Our increased understanding of pro-inflammatory and thrombotic pathophysiology in MPN provides a rational basis for evaluation of in-development MPN therapeutics to reduce thrombosis.
Original language | English (US) |
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Pages (from-to) | 304-313 |
Number of pages | 10 |
Journal | Current Hematologic Malignancy Reports |
Volume | 16 |
Issue number | 3 |
DOIs | |
State | Published - Jun 2021 |
Bibliographical note
Publisher Copyright:© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Keywords
- BCR/ABL negative myeloproliferative neoplasms
- Neutrophils
- P-selectin
- Thrombosis
- Tissue factor
- Vascular inflammation
- Disease Susceptibility
- Signal Transduction
- STAT Transcription Factors/metabolism
- Humans
- Cell Communication
- Thrombosis/diagnosis
- Treatment Outcome
- Myeloproliferative Disorders/complications
- Janus Kinase 2/genetics
- Biomarkers
- Disease Management
- Combined Modality Therapy/adverse effects
- Mutation
- Organ Specificity/genetics
PubMed: MeSH publication types
- Review
- Research Support, Non-U.S. Gov't
- Journal Article