| Autor: |
Ferrone CK; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada., Blydt-Hansen M; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada., Rauh MJ; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2020 Jan 17; Vol. 21 (2). Date of Electronic Publication: 2020 Jan 17. |
| DOI: |
10.3390/ijms21020626 |
| Abstrakt: |
Acquired, inactivating mutations in Tet methylcytosine dioxygenase 2 ( TET2 ) are detected in peripheral blood cells of a remarkable 5%-10% of adults greater than 65 years of age. They impart a hematopoietic stem cell advantage and resultant clonal hematopoiesis of indeterminate potential (CHIP) with skewed myelomonocytic differentiation. CHIP is associated with an overall increased risk of transformation to a hematological malignancy, especially myeloproliferative and myelodysplastic neoplasms (MPN, MDS) and acute myeloid leukemia (AML), of approximately 0.5% to 1% per year. However, it is becoming increasingly possible to identify individuals at greatest risk, based on CHIP mutational characteristics. CHIP, and particularly TET2 -mutant CHIP, is also a novel, significant risk factor for cardiovascular diseases, related in part to hyper-inflammatory, progeny macrophages carrying TET2 mutations. Therefore, somatic TET2 mutations contribute to myeloid expansion and innate immune dysregulation with age and contribute to prevalent diseases in the developed world-cancer and cardiovascular disease. Herein, we describe the impact of detecting TET2 mutations in the clinical setting. We also present the rationale and promise for targeting TET2 -mutant and other CHIP clones, and their inflammatory environment, as potential means of lessening risk of myeloid cancer development and dampening CHIP-comorbid inflammatory diseases. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
