title: Phosphatase of regenerating liver in hematopoietic stem cells and hematological malignancies.
abstract: The phosphatases of regenerating liver (PRLs), consisting PRL1, PRL2 and PRL3, are dual-specificity protein phosphatases that have been implicated as biomarkers and therapeutic targets in several solid tumors. However, their roles in hematological malignancies are largely unknown. Recent findings demonstrate that PRL2 is important for hematopoietic stem cell self-renewal and proliferation. In addition, both PRL2 and PRL3 are highly expressed in some hematological malignancies, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), multiple myeloma (MM) and acute lymphoblastic leukemia (ALL). Moreover, PRL deficiency impairs the proliferation and survival of leukemia cells through regulating oncogenic signaling pathways. While PRLs are potential novel therapeutic targets in hematological malignancies, their exact biological function and cellular substrates remain unclear. This review will discuss how PRLs regulate hematopoietic stem cell behavior, what signaling pathways are regulated by PRLs, and how to target PRLs in hematological malignancies. An improved understanding of how PRLs function and how they are regulated may facilitate the development of PRL inhibitors that are effective in cancer treatment.
authors.affiliation: a Department of Pediatrics, Herman B Wells Center for Pediatric Research; Department of Biochemistry and Molecular Biology , Indiana University School of Medicine ; Indianapolis , IN USA.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Sisi
authors.initials: S
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Gao
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Bai
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D019337:Hematologic Neoplasms / Q000201:enzymology*; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D008115:Liver Regeneration; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010744:Phosphoric Monoester Hydrolases
keywords: PRL; PTP4A; hematological malignancy and therapeutic target; hematopoietic stem cell; oncogenic signaling; self-renewal