Glycogen Synthase Kinase-3 and phospholipase C-beta signalling: Roles and possible interactions in myelodysplastic syndromes and acute myeloid leukemia.

Stefano Ratti, Sara Mongiorgi, Isabella Rusciano, Lucia Manzoli, Matilde Y Follo

Journal: Biochimica et biophysica acta. Molecular cell research 2020;1867(4):118649

PMID: 31954103

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Abstract

GSK-3 and PLCbeta enzymes are responsible for the regulation of several signalling pathways related to many cellular functions. In hematopoietic cells, GSK-3 deficiency is correlated with an MDS-like phenotype and with leukemogenesis, showing a prognostic potential in AML cells. GSK-3 interacts with Wnt or MAPK signalling, but it is also linked to PI3K/Akt/mTOR pathways to regulate cell proliferation and apoptosis of hematopoietic stem cell progenitors. PLCbeta enzymes are involved in cell cycle progression of hematopoietic, MDS/AML and immune cells, through activation of PKC or calcium signalling. Of note, a PLCbeta1/PKCalpha pathway is modulated during MDS pathogenesis, with a specific involvement of the inositides localized in the nucleus. Here we focus on GSK-3 and PLCbeta signalling, describing the many evidences that underline the pivotal role of both GSK-3 and PLCbeta-dependent pathways in MDS/AML, their association with therapy and their possible interactions.

Address: Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, via Irnerio 48, 40126 Bologna, Italy.; Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, via Irnerio 48, 40126 Bologna, Italy. Electronic address: [email protected].

DOI: 10.1016/j.bbamcr.2020.118649