ArticleLeukemia2005
Inhibition of PI3K, mTOR and MEK signaling pathways promotes rapid apoptosis in B-lineage ALL in the presence of stromal cell support.
Article in Leukemia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Ferroptosis in multiple myeloma: molecular mechanisms and therapeutic opportunities.Frontiers in oncology · 2026Review
- PAK1 Mediates Bone Marrow Stromal Cell-Induced Drug Resistance in Acute Myeloid Leukemia via ERK1/2 Signaling Pathway.Frontiers in cell and developmental biology · 2021Article
- Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?Frontiers in immunology · 2020Review
- Activation of WNT/β-catenin signaling results in resistance to a dual PI3K/mTOR inhibitor in colorectal cancer cells harboring PIK3CA mutations.International journal of cancer · 2019Article
- The novel RAGE interactor PRAK is associated with autophagy signaling in Alzheimer's disease pathogenesis.Molecular neurodegeneration · 2016Article
- Activation of mTOR: a culprit of Alzheimer's disease?Neuropsychiatric disease and treatment · 2015Review
- mTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.PloS one · 2014Article
- Role of integrin alpha4 in drug resistance of leukemia.Frontiers in oncology · 2014Review
- Mammalian target of rapamycin (mTOR) activity dependent phospho-protein expression in childhood acute lymphoblastic leukemia (ALL).PloS one · 2013Article
- Article
- Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy.Blood cancer journal · 2012Article
- Review
- Ex vivo rapamycin treatment of human cord blood CD34+ cells enhances their engraftment of NSG mice.Blood cells, molecules & diseases · 2011Article
- Tyrosine dephosphorylation is required for Bak activation in apoptosis.The EMBO journal · 2010Article
- Exploiting cellular pathways to develop new treatment strategies for AML.Cancer treatment reviews · 2010Review
- Article
- Novel molecular and cellular therapeutic targets in acute lymphoblastic leukemia and lymphoproliferative disease.Immunologic research · 2008Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Bone marrow stromal cells are essential for the differentiation, survival and proliferation of normal and leukemic human B-lineage cells. Leukemic cells require stromal cell support for optimal proliferation and apoptotic resistance. Stromal cell contact can promote resistance to chemotherapeutic agents. In this study, we have made use of small molecular weight inhibitors and an established stromal cell-dependent pre-B-ALL cell line, BLIN-2, to investigate the role of the MAP kinase, PI3K/Akt, JAK/STAT and mTOR pathways in the promotion of leukemic cell growth in the presence of stromal cell support. Treatment with PI3K+JAK, PI3K+MEK, or MEK+JAK inhibitor combinations resulted in an inhibition of proliferation as measured by DNA synthesis. However, only inhibition of both PI3K and MEK or both mTOR and MEK resulted in a dramatic increase in the number of annexinV(+)/PI(+) apoptotic events within a 24 h period. Our data suggest that stromal cell-mediated apoptotic protection in B-lineage ALL is mediated by PI3K/mTOR and MEK via a synergistic mechanism(s).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.