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Review
. 2023 Aug;18(4):105-112.
doi: 10.1007/s11899-023-00697-5. Epub 2023 May 24.

Clonal Hematopoiesis in Myeloproliferative Neoplasms Confers a Predisposition to both Thrombosis and Cancer

Tiziano Barbui  1 , Antonello Gavazzi  2 , Edoardo Sciatti  3 , Maria Chiara Finazzi  4 , Arianna Ghirardi  2 , Greta Carioli  2 , Alessandra Carobbio  2
Affiliations
Review

Clonal Hematopoiesis in Myeloproliferative Neoplasms Confers a Predisposition to both Thrombosis and Cancer

Tiziano Barbui et al. Curr Hematol Malig Rep. 2023 Aug.

Abstract

Purpose of review: This review focuses on vascular complications associated with chronic myeloproliferative neoplasms (MPN) and more specifically aims to discuss the clinical and biological evidence supporting the existence of a link between clonal hematopoiesis, cardiovascular events (CVE), and solid cancer (SC).

Recent findings: The MPN natural history is driven by uncontrolled clonal myeloproliferation sustained by acquired somatic mutations in driver (JAK2, CALR, and MPL) and non-driver genes, involving epigenetic (e.g., TET2, DNMT3A) regulators, chromatin regulator genes (e.g., ASXL1, EZH2), and splicing machinery genes (e.g., SF3B1). The genomic alterations and additional thrombosis acquired risk factors are determinants for CVE. There is evidence that clonal hematopoiesis can elicit a chronic and systemic inflammation status that acts as driving force for the development of thrombosis, MPN evolution, and second cancer (SC). This notion may explain the mechanism that links arterial thrombosis in MPN patients and subsequent solid tumors. In the last decade, clonal hematopoiesis of indeterminate potential (CHIP) has been detected in the general population particularly in the elderly and initially found in myocardial infarction and stroke, rising the hypothesis that the inflammatory status CHIP-associated could confer predisposition to both cardiovascular diseases and cancer. In summary, clonal hematopoiesis in MPN and CHIP confer a predisposition to cardiovascular events and cancer through chronic and systemic inflammation. This acquisition could open new avenues for antithrombotic therapy both in MPNs and in general population by targeting both clonal hematopoiesis and inflammation.

Keywords: Cancer; Clonal hematopoiesis of indeterminate potential; Disease progression; Inflammation; Myeloproliferative neoplasms; Thrombosis.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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