TY - JOUR
T1 - Clonal hematopoietic mutations linked to platelet traits and the risk of thrombosis or bleeding
AU - Veninga, Alicia
AU - De Simone, Ilaria
AU - Heemskerk, Johan W. M.
AU - Ten Cate, Hugo
AU - van der Meijden, Paola E. J.
N1 - Funding Information:
AV is supported by the Dutch Landsteiner Foundation for Blood Transfusion Research (1711). IDS is supported by a joint PhD scholarship of Maastricht and Reading Universities, and by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement n. 766118.
Publisher Copyright:
©2020 Ferrata Storti Foundation
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Platelets are key elements in thrombosis, particularly in atherosclerosis-associated arterial thrombosis (atherothrombosis), and hemostasis. Megakaryocytes in the bone marrow, differentiated from hematopoietic stem cells are generally considered as a uniform source of platelets. However, recent insights into the causes of malignancies, including essential thrombocytosis, indicate that not only inherited but also somatic mutations in hematopoietic cells are linked to quantitative or qualitative platelet abnormalities. In particular cases, these form the basis of thrombo-hemorrhagic complications regularly observed in patient groups. This has led to the concept of clonal hematopoiesis of indeterminate potential (CHIP), defined as somatic mutations caused by clonal expansion of mutant hematopoietic cells without evident disease. This concept also provides clues regarding the importance of platelet function in relation to cardiovascular disease. In this summative review, we present an overview of genes associated with clonal hematopoiesis and altered platelet production and/or functionality, like mutations in JAK2. We consider how reported CHIP genes can influence the risk of cardiovascular disease, by exploring the consequences for platelet function related to (athero)thrombosis, or the risk of bleeding. More insight into the functional consequences of the CHIP mutations may favor personalized risk assessment, not only with regard to malignancies but also in relation to thrombotic vascular disease.
AB - Platelets are key elements in thrombosis, particularly in atherosclerosis-associated arterial thrombosis (atherothrombosis), and hemostasis. Megakaryocytes in the bone marrow, differentiated from hematopoietic stem cells are generally considered as a uniform source of platelets. However, recent insights into the causes of malignancies, including essential thrombocytosis, indicate that not only inherited but also somatic mutations in hematopoietic cells are linked to quantitative or qualitative platelet abnormalities. In particular cases, these form the basis of thrombo-hemorrhagic complications regularly observed in patient groups. This has led to the concept of clonal hematopoiesis of indeterminate potential (CHIP), defined as somatic mutations caused by clonal expansion of mutant hematopoietic cells without evident disease. This concept also provides clues regarding the importance of platelet function in relation to cardiovascular disease. In this summative review, we present an overview of genes associated with clonal hematopoiesis and altered platelet production and/or functionality, like mutations in JAK2. We consider how reported CHIP genes can influence the risk of cardiovascular disease, by exploring the consequences for platelet function related to (athero)thrombosis, or the risk of bleeding. More insight into the functional consequences of the CHIP mutations may favor personalized risk assessment, not only with regard to malignancies but also in relation to thrombotic vascular disease.
KW - WISKOTT-ALDRICH SYNDROME
KW - ACUTE MYELOID-LEUKEMIA
KW - MYELOPROLIFERATIVE NEOPLASMS
KW - ACCELERATES ATHEROSCLEROSIS
KW - MEGAKARYOCYTE DEVELOPMENT
KW - MYELODYSPLASTIC SYNDROMES
KW - DEFICIENCY
KW - MEGAKARYOPOIESIS
KW - GENE
KW - PROTEIN
U2 - 10.3324/haematol.2019.235994
DO - 10.3324/haematol.2019.235994
M3 - (Systematic) Review article
C2 - 32554558
SN - 0390-6078
VL - 105
SP - 2020
EP - 2031
JO - Haematologica-the Hematology Journal
JF - Haematologica-the Hematology Journal
IS - 8
ER -