title: Inositide-dependent signaling pathways as new therapeutic targets in myelodysplastic syndromes.
abstract: BACKGROUND
  Nuclear inositide signaling pathways specifically regulate cell proliferation and differentiation. Interestingly, the modulation of nuclear inositides in hematological malignancies can differentially affect erythropoiesis or myelopoiesis. This is particularly important in patients with myelodysplastic syndromes (MDS), who show both defective erythroid and myeloid differentiation, as well as an increased risk of evolution into acute myeloid leukemia (AML).
  
  
  METHODS
  This review focuses on the structure and function of specific nuclear inositide enzymes, whose impairment could be linked with disease pathogenesis and cancer. The authors, stemming from literature and published data, discuss and describe the role of nuclear inositides, focusing on specific enzymes and demonstrating that targeting these molecules could be important to develop innovative therapeutic approaches, with particular reference to MDS treatment.
  
  
  CONCLUSIONS
  Demethylating therapy, alone or in combination with other drugs, is the most common and current therapy for MDS patients. Nuclear inositide signaling molecules have been demonstrated to be important in hematopoietic differentiation and are promising new targets for developing a personalized MDS therapy. Indeed, these enzymes can be ideal targets for drug design and their modulation can have several important downstream effects to regulate MDS pathogenesis and prevent MDS progression to AML.
authors.affiliation: a Cellular Signalling Laboratory, Institute of Human Anatomy, Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mongiorgi
authors.affiliation: b Institute of Hematology "L e A Seràgnoli" , S. Orsola-Malpighi Hospital , Bologna , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Finelli
authors.affiliation: c School of Life Sciences , Ulsan National Institute of Science and Technology , Ulsan , Republic of Korea.
authors.forename: Yong Ryoul
authors.initials: YR
authors.lastname: Yang
authors.affiliation: b Institute of Hematology "L e A Seràgnoli" , S. Orsola-Malpighi Hospital , Bologna , Italy.|d Hematology and Transplant Center , AORMN , Pesaro , Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Clissa
authors.affiliation: e Department of Microbiology & Immunology, Brody School of Medicine , East Carolina University , Greenville , NC , USA.
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
authors.affiliation: a Cellular Signalling Laboratory, Institute of Human Anatomy, Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Billi
authors.affiliation: a Cellular Signalling Laboratory, Institute of Human Anatomy, Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Manzoli
authors.affiliation: c School of Life Sciences , Ulsan National Institute of Science and Technology , Ulsan , Republic of Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: a Cellular Signalling Laboratory, Institute of Human Anatomy, Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.affiliation: a Cellular Signalling Laboratory, Institute of Human Anatomy, Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy.
authors.forename: Matilde Y
authors.initials: MY
authors.lastname: Follo
mesh_terms: D000818:Animals; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000517:prevention & control; D058990:Molecular Targeted Therapy; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D010716:Phosphatidylinositols / Q000378:metabolism*; D057285:Precision Medicine; D015398:Signal Transduction
chemical_list: D010716:Phosphatidylinositols
keywords: Myelodysplastic syndromes; PI-PLCbeta1; PI-PLCgamma1; PI3K/Akt/mTOR; nuclear inositides