The Important Role of STAT3 in Chronic Lymphocytic Leukaemia Biology


BOUDNÝ Miroslav TRBUŠEK Martin

Year of publication 2020
Type Article in Periodical
Magazine / Source Klinická onkologie
MU Faculty or unit

Faculty of Medicine

Keywords STAT3; STAT; chronic lymphocytic leukaemia; therapy; microenvironment; ibrutinib; con-stitutive activation; leukaemia
Description Background: Signal transducer and activator of transcription (STAT) proteins are cytoplasmic tran-scription factors that transmit the signal of cytokines, hormones and growth factors. STAT pro-teins control fundamental cellular processes including survival, proliferation and differentiation.Inappropriate activation of STATs might contribute to cellular transformation and leukaemogene-sis. About 70% of all solid and haematological tumours exhibit aberrant STAT3 expression and/ or activation, highlighting its essential role in tumourigenesis. Aberrant STAT3 activation has been found in several solid tumours and haematologic malignancies. Importantly, constitutive activa-tion of STAT proteins has been found in several leukaemias including acute myeloid leukaemia, acute promyelocytic leukaemia, acute lymphoblastic leukaemia, chronic myeloid leukaemia and chronic lymphocytic leukaemia (CLL). Constitutively activated STAT3 plays an important role in CLL bio logy. CLL cells harbour constitutive phosphorylation on S727 and acetylation on K685 and transient phosphorylation on Y705 residues. Moreover, STAT3 messenger RNA expression is signi-ficantly higher in CLL cells compared to healthy B-lymphocytes. Interestingly, STAT3 inhibition was disclosed as an important by-product of ibrutinib treatment in CLL patients. Purpose: The purpose of this review is to describe the consequences of STAT3 dysregulation in CLL cells. Here, we discuss aberrantly modified processes by STAT3 activation in CLL cells such as proliferation, apoptosis, B cell receptor signalling, cytokine secretion, immune checkpoint regulation, microRNA regulation, free fatty acid metabolism and electron transport chain in the mitochondria.
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