title: The emerging role of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in normal myelopoiesis and leukemogenesis.
abstract: The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway mediates diverse and important physiological cell functions which include proliferation, differentiation, survival, motility, autophagy, and metabolism. However, dysregulated PI3K/Akt/mTOR signaling has been documented in a wide range of neoplasias, including malignant hematological disorders. It is now emerging that this signaling network plays a key role during normal hematopoiesis, a tightly regulated process resulting in the formation of all blood lineages. Blood cell development encompasses a complex series of events which are mainly regulated by actions of cytokines, a family of extracellular ligands which stimulate many biological responses in a wide array of cell types. Hematopoiesis is strictly dependent on the correct function of the bone marrow microenvironment (BMM), as BMM cells secrete most of the cytokines. Several of these cytokines activate the PI3K/Akt/mTOR signaling network and regulate proliferation, survival, and differentiation events during hematopoiesis. Here, we review the evidence that links the signals emanating from the PI3K/Akt/mTOR cascade with the functions of hematopoietic stem cells and the process of myelopoiesis, including lineage commitment. We then highlight the emerging role played by aberrant PI3K/Akt/mTOR signaling during leukemogenesis.
authors.affiliation: Department of Human Anatomy, University of Bologna, via Irnerio 48, 40126 Bologna, Italy. alberto.martelli@unibo.it
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Martelli
authors.forename: Camilla
authors.initials: C
authors.lastname: Evangelisti
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiarini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Grimaldi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cappellini
authors.forename: Andrea
authors.initials: A
authors.lastname: Ognibene
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
mesh_terms: D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D038042:Myelopoiesis / Q000235:genetics* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human