Glycogen Synthase Kinase-3 and Phospholipase C-beta Signalling: Roles and Possible Interactions in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Biochim Biophys Acta Mol Cell Res. 2020 Apr;1867(4):118649. doi: 10.1016/j.bbamcr.2020.118649. Epub 2020 Jan 15.

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.

Keywords: GSK-3; Leukemia; Myelodysplastic syndromes; PLCbeta; PLCbeta1; Signalling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 / physiology
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / enzymology*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / enzymology*
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / metabolism
  • Phospholipase C beta / metabolism*
  • Phospholipase C beta / physiology
  • Signal Transduction*

Substances

  • Glycogen Synthase Kinase 3
  • Phospholipase C beta