The phenomenon of clonal hematopoiesis: etiology, classification and its prognostic role

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Abstract

   The phenomenon of clonal hematopoiesis (CH) has been the subject of intensive research since 2014, facilitated by the development of high‑throughput sequencing technology. with age, the prevalence of CH increases, which is associated with an increased risk of hematological and cardiovascular diseases, as well as with overall mortality. The occurrence of somatic mutations in hematopoietic stem cells is the primary mechanism of CH, as a result of which the balance between cell division and differentiation is disrupted, which leads to the expansion of cell clones with specific genetic changes. The article reviews the concept of CH and its various types, including clonal hematopoiesis of indeterminate and tumorigenic potential, as well as associated conditions such as idiopathic cytopenia of undetermined significance, clonal cytopenia of undetermined significance, and idiopathic dysplasia of undetermined significance. Clonal hematopoiesis is defined by the presence of somatic mutations in myeloid‑related genes (commonly DNMT3A, TET2, and ASXL1) in hematopoietic cells, which can be present in both healthy people and patients with hematological neoplasia. The importance of distinguishing between different CH forms depending on their prognostic significance and the potential risk of transformation into malignant neoplasms is emphasized. Mutations associated with CH may increase the risk of cardiovascular diseases, type 2 diabetes mellitus, chronic obstructive pulmonary disease, venous thrombosis, and myeloid and lymphoid neoplasms. In conclusion, the need to develop formalized diagnostic criteria and predictive models for risk stratification in individuals with various CH forms is emphasized, which can significantly affect diagnostic approaches and the possibility of treating these conditions.

About the authors

E. O. Kunevich

Leningrad Regional Clinical Hospital

Author for correspondence.
Email: kunevich17@gmail.com
ORCID iD: 0000-0002-1706-6642

Evgeniy Olegovich Kunevich

194291;  lit. A, Build. 1, 45 Lunacharskogo Prospekt; Saint Petersburg

Russian Federation

M. A. Mikhaleva

Russian Research Institute of Hematology and Transfusiology, Federal Medical and Biological Agency

ORCID iD: 0000-0002-2135-2051

191024; 16 2nd Sovetskaya St.; Saint Petersburg

Russian Federation

O. B. Krysyuk

Russian Research Institute of Hematology and Transfusiology, Federal Medical and Biological Agency; Saint-Petersburg State University

ORCID iD: 0000-0002-5083-915X

191024; 16 2nd Sovetskaya St.; 199034; 7–9 Universitetskaya Naberezhnaya; Saint Petersburg

Russian Federation

A. N. Bogdanov

Saint-Petersburg State University; City hospital No. 40

ORCID iD: 0000-0003-1964-3690

199034; 7–9 Universitetskaya Naberezhnaya; Saint Petersburg; 197706; 9 Borisova St.; Saint Petersburg; Sestroretsk 

Russian Federation

A. A. Zhernyakova

Russian Research Institute of Hematology and Transfusiology, Federal Medical and Biological Agency

ORCID iD: 0000-0001-9260-3025

191024; 16 2nd Sovetskaya St.; Saint Petersburg

Russian Federation

S. V. Voloshin

Leningrad Regional Clinical Hospital; Military Medical Academy named after S. M. Kirov, Ministry of Defense of Russia

ORCID iD: 0000-0003-1784-0375

194291;  lit. A, Build. 1, 45 Lunacharskogo Prospekt; 194044; 6 Akademika Lebedeva St.; Saint Petersburg

Russian Federation

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-36928 от  21.07.2009.