TY - JOUR
T1 - The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling network and the control of normal myelopoiesis
AU - Martelli, Alberto M.
AU - Chiarini, Francesca
AU - Evangelisti, Camilla
AU - Grimaldi, Cecilia
AU - Ognibene, Andrea
AU - Manzoli, Lucia
AU - Billi, Anna Maria
AU - McCubrey, James A.
PY - 2010/5
Y1 - 2010/5
N2 - The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role in cell growth, proliferation, differentiation, and survival under physiological conditions. Aberrant regulation of the PI3K/Akt/mTOR signal transduction network has been observed in a wide range of neoplasias, including malignant hematological disorders. This observation suggests that this signaling cascade could also play a critical role during normal hematopoiesis, a highly regulated process which results in the formation of all blood lineages. The development of blood cells comprises a complex series of events which are mainly regulated through the actions of cytokines, a large family of extracellular ligands than can stimulate many biological responses in a wide array of cell types. Several of these cytokines are known to activate the PI3K/Akt/mTOR signal transduction network and thus regulate proliferation, survival, and differentiation events during hematopoiesis. Moreover, hematopoiesis is strictly dependent on the correct functions of the bone marrow microenvironment. Here, we review the evidence which links the signals emanating from the PI3K/Akt/mTOR cascade with the functions of hematopoietic stem cells and the process of lineage commitment, which then gives rise to myeloid lineage-restricted cells. We then further highlight the key role played by the PI3K/Akt/mTOR network during erythropoiesis, megakaryocytopoiesis, and granulo-cytopoiesis/monocytopoiesis.
AB - The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role in cell growth, proliferation, differentiation, and survival under physiological conditions. Aberrant regulation of the PI3K/Akt/mTOR signal transduction network has been observed in a wide range of neoplasias, including malignant hematological disorders. This observation suggests that this signaling cascade could also play a critical role during normal hematopoiesis, a highly regulated process which results in the formation of all blood lineages. The development of blood cells comprises a complex series of events which are mainly regulated through the actions of cytokines, a large family of extracellular ligands than can stimulate many biological responses in a wide array of cell types. Several of these cytokines are known to activate the PI3K/Akt/mTOR signal transduction network and thus regulate proliferation, survival, and differentiation events during hematopoiesis. Moreover, hematopoiesis is strictly dependent on the correct functions of the bone marrow microenvironment. Here, we review the evidence which links the signals emanating from the PI3K/Akt/mTOR cascade with the functions of hematopoietic stem cells and the process of lineage commitment, which then gives rise to myeloid lineage-restricted cells. We then further highlight the key role played by the PI3K/Akt/mTOR network during erythropoiesis, megakaryocytopoiesis, and granulo-cytopoiesis/monocytopoiesis.
KW - Differentiation
KW - Hematopoietic stem cells
KW - PI3K/Akt/mTOR
KW - Proliferation
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=77953043118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953043118&partnerID=8YFLogxK
M3 - Article
C2 - 20238304
AN - SCOPUS:77953043118
VL - 25
SP - 669
EP - 680
JO - Histology and Histopathology
JF - Histology and Histopathology
SN - 0213-3911
IS - 5
ER -