Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2017 Sep 29

PMID 28955303

Citations 25

Authors

Isabelle Plo

Christine Bellanne-Chantelot

Matthieu Mosca

Stefania Mazzi

Caroline Marty

William Vainchenker

Affiliations

Soon will be listed here.

Abstract

Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity () and loss-of-function (LOF) activity of negative regulators () or the extrinsic MPL signaling by GOF mutations leading to increased TPO synthesis. Alternatively, thrombocytosis may paradoxically result from mutations of leading to an abnormal MPL trafficking, inducing increased TPO levels by alteration of its clearance. In contrast, thrombocytopenia can also result from LOF or mutations, which cause a complete defect in MPL trafficking to the cell membrane, impaired MPL signaling or stability, defects in the TPO/MPL interaction, or an absence of TPO production.

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