Benzoquinone, a leukemogenic metabolite of benzene, catalytically inhibits the protein tyrosine phosphatase PTPN2 and alters STAT1 signaling.

ABSTRACT: Protein tyrosine phosphatase, nonreceptor type 2 (PTPN2) is mainly expressed in hematopoietic cells, where it negatively regulates growth factor and cytokine signaling. PTPN2 is an important regulator of hematopoiesis and immune/inflammatory responses, as evidenced by loss-of-function mutations of PTPN2 in leukemia and lymphoma and knockout mice studies. Benzene is an environmental chemical that causes hematological malignancies, and its hematotoxicity arises from its bioactivation in the bone marrow to electrophilic metabolites, notably 1,4-benzoquinone, a major hematotoxic benzene metabolite. Although the molecular bases for benzene-induced leukemia are not well-understood, it has been suggested that benzene metabolites alter topoisomerases II function and thereby significantly co

SUBMITTER: Duval R 

PROVIDER: S-EPMC6699853 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature