Targeting PRL phosphatases in hematological malignancies

Expert Opin Ther Targets. 2024 Apr 26:1-13. doi: 10.1080/14728222.2024.2344695. Online ahead of print.

Abstract

Introduction: Phosphatase of regenerating liver (PRL) family proteins, also known as protein tyrosine phosphatase 4A (PTP4A), have been implicated in many types of cancers. The PRL family of phosphatases consists of three members, PRL1, PRL2, and PRL3. PRLs have been shown to harbor oncogenic potentials and are highly expressed in a variety of cancers. Given their roles in cancer progression and metastasis, PRLs are potential targets for anticancer therapies. However, additional studies are needed to be performed to fully understand the roles of PRLs in blood cancers.

Areas covered: In this review, we will summarize recent studies of PRLs in normal and malignant hematopoiesis, the role of PRLs in regulating various signaling pathways, and the therapeutic potentials of targeting PRLs in hematological malignancies. We will also discuss how to improve current PRL inhibitors for cancer treatment.

Expert opinion: Although PRL inhibitors show promising therapeutic effects in preclinical studies of different types of cancers, moving PRL inhibitors from bench to bedside is still challenging. More potent and selective PRL inhibitors are needed to target PRLs in hematological malignancies and improve treatment outcomes.

Keywords: AML; Phosphatase of regenerating liver; hematological malignancies; hematopoietic stem cells; leukemia; oncogenic signaling; protein tyrosine phosphatase; therapeutic target.

Publication types

  • Review