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The thrombopoietin receptor: revisiting the master regulator of platelet production

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JournalPlatelets
DateSubmitted - 23 Dec 2020
DateAccepted/In press - 28 Apr 2021
DateE-pub ahead of print (current) - 7 Jun 2021
Number of pages9
Pages (from-to)1-9
Early online date7/06/21
Original languageEnglish

Abstract

Thrombopoietin (TPO) and its receptor, MPL, are the primary regulators of platelet production and critical for hematopoietic stem cell (HSC) maintenance. Since TPO was first cloned in 1994, the physiological and pathological roles of TPO and MPL have been well characterized, culminating in the first MPL agonists being approved for the treatment of chronic immune thrombocytopenia in 2008. Dysregulation of the TPO-MPL signaling axis contributes to the pathogenesis of hematological disorders: decreased expression or function results in severe thrombocytopenia progressing to bone marrow failure, while hyperactivation of MPL signaling, either by mutations in the receptor or associated Janus kinase 2 (JAK2), results in pathological myeloproliferation. Despite its importance, it was only recently that the long-running debate over the mechanism by which TPO binding activates MPL has been resolved. This review will cover key aspects of TPO and MPL structure and function and their importance in receptor activation, discuss how these are altered in hematological disorders and consider how a greater understanding could lead to the development of better-targeted and more efficacious therapies.

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© 2021 The Author(s). Published with
license by Taylor & Francis Group, LLC.

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