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Review
. 2021 Nov;19(6):518-532.
doi: 10.2450/2020.0197-20. Epub 2020 Dec 16.

Erythrocytosis: genes and pathways involved in disease development

Jernej Gašperšič  1 , Aleša Kristan  1 , Tanja Kunej  2 , Irena Preložnik Zupan  3   4 , Nataša Debeljak  1
Affiliations
Review

Erythrocytosis: genes and pathways involved in disease development

Jernej Gašperšič et al. Blood Transfus. 2021 Nov.

Abstract

Erythrocytosis is a blood disorder characterised by an increased red blood cell mass. The most common causes of erythrocytosis are acquired and caused by diseases and conditions that are accompanied by hypoxaemia or overproduction of erythropoietin. More rarely, erythrocytosis has a known genetic background, such as for polycythaemia vera and familial erythrocytosis. The majority of cases of polycythaemia vera are associated with acquired variants in JAK2, while familial erythrocytosis is a group of congenital disorders. Familial erythrocytosis type 1 is associated with hypersensitivity to erythropoietin (variants in EPOR), types 2-5 with defects in oxygen-sensing pathways (variants in VHL, EGLN1, EPAS1, EPO), and types 6-8 with an increased affinity of haemoglobin for oxygen (variants in HBB, HBA1, HBA2, BPGM). Due to a heterogenic genetic background, the causes of disease are not fully discovered and in more than 70% of patients the condition remains labelled idiopathic.The transfer of next-generation sequencing into clinical practice is becoming a reality enabling detection of various variants in a single rapid test. In this review, we describe the current research on erythrocytosis gene variants and the mechanisms associated with disease development, along with the currently used diagnostic tests.

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Conflict of interest statement

The Authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Role of erythropoietin and other cytokines in erythropoiesis
Scheme of the maturation and differentiation of stem cells to fully developed erythrocytes. The cytokines interleukin (IL)-1, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem-cell factor (SCF) regulate the development of haematopoietic stem cells into proerythroblasts. Cytokines SCF, IL-3, GM-SCF, and erythropoietin (EPO) further evolve the proerythroblasts to erythrocytes. EPO influences the differentiation of cells expressing EPO receptor (EPOR) on the cell surface, up to the formation of reticulocytes. Erythroblasts evolve into normoblasts, which lose the nucleus and develop into reticulocytes, and later into erythrocytes.
Figure 2
Figure 2
Pathways associated with erythrocytosis (A) The genes involved in the hypoxia-inducible factor (HIF) – erythropoietin (EPO) pathway in the kidneys. (B) Genes involved in the EPO – erythropoietin receptor (EPOR) signalling pathway in erythroid progenitors. (C) Genes affecting haemoglobin-oxygen affinity in erythrocytes.
Figure 2
Figure 2
Pathways associated with erythrocytosis (A) The genes involved in the hypoxia-inducible factor (HIF) – erythropoietin (EPO) pathway in the kidneys. (B) Genes involved in the EPO – erythropoietin receptor (EPOR) signalling pathway in erythroid progenitors. (C) Genes affecting haemoglobin-oxygen affinity in erythrocytes.
Figure 2
Figure 2
Pathways associated with erythrocytosis (A) The genes involved in the hypoxia-inducible factor (HIF) – erythropoietin (EPO) pathway in the kidneys. (B) Genes involved in the EPO – erythropoietin receptor (EPOR) signalling pathway in erythroid progenitors. (C) Genes affecting haemoglobin-oxygen affinity in erythrocytes.
See this image and copyright information in PMC

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