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

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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.

Summary

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.

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Funding

This work was supported by the “RICO” project, BCC Milano, Italy.

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Authors and Affiliations

  1. FROM Research Foundation, Papa Giovanni XXIII Hospital, Piazza O.M.S, 1 - 24127, Bergamo (BG), Italy

    Tiziano Barbui, Antonello Gavazzi, Arianna Ghirardi, Greta Carioli & Alessandra Carobbio

  2. Cardiovascular Department, Cardiology Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy

    Edoardo Sciatti

  3. Department of Oncology-Hematology, University of Milan and Papa Giovanni XXIII Hospital, Bergamo, Italy

    Maria Chiara Finazzi

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  1. Tiziano Barbui
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Barbui, T., Gavazzi, A., Sciatti, E. et al. Clonal Hematopoiesis in Myeloproliferative Neoplasms Confers a Predisposition to both Thrombosis and Cancer. Curr Hematol Malig Rep 18, 105–112 (2023). https://doi.org/10.1007/s11899-023-00697-5

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