Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway has been observed in different types of leukemia, including CML, acute myeloid leukemia, and acute lymphoblastic leukemia.
Taken together, these results reveal an unrecognized function of MTE in inhibiting the proliferation and inducing the apoptosis of T-ALL cells, and identify a pathway of PTEN/PI3K/AKT/mTOR for the effects of MTE on leukemia therapy.
We show that mouse thymic stromal lymphopoietin does not stimulate the downstream pathways (JAK/STAT5 and PI3K/AKT/mTOR) activated by the human cytokine in primary high-risk leukemia with overexpression of the receptor component.
These data provide a molecular rationale for using BH3 mimetics in combination with PI3K inhibitors to treat leukemia, especially in the case of an oncogenic signaling refractory to Tyrosine Kinase inhibitors.
In the present study, we have shown for the first time that HBA decreased the expression of phosphotidylinositol-3 kinase (PI3K) p110α and p85α and caused significant downregulation of pAKT and of NFκB using human leukemia and breast cancer cells as in vitro models.
Our study reveals a novel role for RhoA/ROCK1/PTEN/PI3K/Akt signaling in the regulation of mitochondrial translocation of cofilin and apoptosis and suggests MC-3129 as a potential drug for the treatment of human leukemia.
The Proviral Integration site of Moloney murine leukemia virus (PIM) serine/threonine protein kinases are overexpressed in many hematologic and solid tumor malignancies and play central roles in intracellular signaling networks important in tumorigenesis, including the Janus kinase-signal transducer and activator of transcription (JAK/STAT) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways.
Conclusively, this study shed lights on the role of c-Myc oncoprotein in acute leukemia cells sensitivity to PI3K inhibitor and outlined that the combination of c-Myc inhibitor and CAL-101 may be a promising therapeutic approach in leukemia.
The p110α isoform of PI3K (encoded by Pik3ca) is an essential effector of oncogenic KRAS in murine lung tumors, but it is unknown whether p110α contributes to leukemia.
Interestingly, recent research has linked the PIM kinases to the PI3K/AKT/mTOR pathway in several types of cancers, but their connection in ovarian cancer has not been studied yet.
To investigate the presence of mutations in the points most frequent for mutations (hotspot mutations) in phosphatidylinositol-3-kinase (PI3K), Janus kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1), which are involved in leukemia and other cancers, in a population of Brazilian MDS patients.
Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with nilotinib against BCR-ABL-positive leukemia cells involves the ABL kinase domain mutation.
UA could induce the differentiation of U937 cells by activating the PI3K/Akt pathway, and it could be a potential candidate as a differentiation-inducing agent for the therapy of leukemia.
Mutations in this pathway and upstream signaling molecules can alter sensitivity to small molecule inhibitors targeting components of this cascade as well as to inhibitors targeting other key pathways (for example, phosphatidylinositol 3 kinase (PI3K)/phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/Akt/mammalian target of rapamycin (mTOR)) activated in leukemia.
Intrigued by the constant activation of PI3K in leukemia, this study aimed to investigate the effects of BKM120, as the excelled member of pan PI3K inhibitors, in a panel of hematologic malignant cell lines.
We observed a growth-promoting effect in tumor cells and an essential function in natural killer (NK) cell-mediated tumor surveillance: Abelson-transformed PI3Kdelta-deficient cells induced leukemia in RAG2-deficient mice with an increased latency, indicating that PI3Kdelta accelerated leukemia progression in vivo.
Suppression of phosphatase and a tensin homolog deleted on chromosome 10 (PTEN) gene expression leading to activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway has been observed in many cancers including leukemia, making the PTEN gene and PI3K/Akt pathway a central target for cancer therapy.
Tetrandrine and cepharanthine induce apoptosis through caspase cascade regulation, cell cycle arrest, MAPK activation and PI3K/Akt/mTOR signal modification in glucocorticoid resistant human leukemia Jurkat T cells.