title: NOTCH and phosphatidylinositide 3-kinase/phosphatase and tensin homolog deleted on chromosome ten/AKT/mammalian target of rapamycin (mTOR) signaling in T-cell development and T-cell acute lymphoblastic leukemia.
abstract: Activating mutations in NOTCH1 consitute the most prominent genetic abnormality in T-cell acute lymphoblastic leukemia (T-ALL). However, most T-ALL cell lines with NOTCH1 mutations are resistant to treatment with γ-secretase inhibitors (GSIs). The spotlight is now shifting to the phosphatidylinositide 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome ten (PTEN)/AKT/mammalian target of rapamycin (mTOR) pathway as another key potential target. These two signaling routes are deregulated in many types of cancer. In this review we discuss these two pathways with respect to their signaling mechanisms, functions during T-cell development, and their mutual roles in the development of T-ALL.
authors.affiliation: Department of Hematology, The Central Hospital of Taian, Taian, Shandong, P R China. dmguo001@yahoo.com.cn
authors.forename: Dongmei
authors.initials: D
authors.lastname: Guo
authors.forename: Qingliang
authors.initials: Q
authors.lastname: Teng
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ji
mesh_terms: D000818:Animals; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D058990:Molecular Targeted Therapy; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051880:Receptors, Notch; D058570:TOR Serine-Threonine Kinases; C494929:PTEN protein, human