Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment.

[1]  M. Konopleva,et al.  Regulation of HIF-1α signaling and chemoresistance in acute lymphocytic leukemia under hypoxic conditions of the bone marrow microenvironment , 2012, Cancer biology & therapy.

[2]  J. E. Robinson,et al.  A potential therapeutic target for FLT3-ITD AML: PIM1 kinase. , 2012, Leukemia research.

[3]  Charles P. Lin,et al.  Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features. , 2011, Blood.

[4]  K. Baggerly,et al.  Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment. , 2010, Blood.

[5]  D. Campana,et al.  Pronounced Hypoxia in Models of Murine and Human Leukemia: High Efficacy of Hypoxia-Activated Prodrug PR-104 , 2011, PloS one.

[6]  M. Levis,et al.  Further Activation of FLT3 Mutants by FLT3 Ligand , 2011, Oncogene.

[7]  W. Wiktor-Jedrzejczak,et al.  Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. , 2011, Blood.

[8]  M. Konopleva,et al.  Leukemia stem cells and microenvironment: biology and therapeutic targeting. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  M. Konopleva,et al.  Phase I study of sorafenib in patients with refractory or relapsed acute leukemias , 2011, Haematologica.

[10]  Deepak Sampath,et al.  Pharmacokinetic-Pharmacodynamic Modeling of Tumor Growth Inhibition and Biomarker Modulation by the Novel Phosphatidylinositol 3-Kinase Inhibitor GDC-0941 , 2010, Drug Metabolism and Disposition.

[11]  M. Andreeff,et al.  Physiological hypoxia promotes lipid raft and PI3K-dependent activation of MAPK 42/44 in leukemia cells , 2010, Leukemia.

[12]  J. McCubrey,et al.  The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients , 2010, Oncotarget.

[13]  Pernilla Eliasson,et al.  The hematopoietic stem cell niche: Low in oxygen but a nice place to be , 2010, Journal of cellular physiology.

[14]  M. Konopleva,et al.  Selective FLT3 inhibitor FI-700 neutralizes Mcl-1 and enhances p53-mediated apoptosis in AML cells with activating mutations of FLT3 through Mcl-1/Noxa axis , 2010, Leukemia.

[15]  Dexin Kong,et al.  Advances in development of phosphatidylinositol 3-kinase inhibitors. , 2009, Current medicinal chemistry.

[16]  P. Workman,et al.  Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941 , 2009, Molecular Cancer Therapeutics.

[17]  M. Eilers,et al.  Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation. , 2009, Blood.

[18]  E. Estey,et al.  Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. , 2009, Blood.

[19]  A. Tee,et al.  Mammalian target of rapamycin complex 1: signalling inputs, substrates and feedback mechanisms. , 2009, Cellular signalling.

[20]  David S. Park,et al.  DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses , 2009, Proceedings of the National Academy of Sciences.

[21]  Lisa S. Chen,et al.  Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. , 2008, Blood.

[22]  M. Salto‐Tellez,et al.  Potential roles for the PIM1 kinase in human cancer - a molecular and therapeutic appraisal. , 2008, European journal of cancer.

[23]  Gary Box,et al.  The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer . , 2008, Journal of medicinal chemistry.

[24]  J. Griffin,et al.  Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells. , 2008, Blood.

[25]  M. Warr,et al.  Unique biology of Mcl-1: therapeutic opportunities in cancer. , 2008, Current molecular medicine.

[26]  M. Konopleva,et al.  Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. , 2008, Journal of the National Cancer Institute.

[27]  F. Lee,et al.  YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-κB signaling to HIF-1α accumulation during hypoxia , 2007, Oncogene.

[28]  G. Mills,et al.  Activation of integrin-linked kinase is a critical prosurvival pathway induced in leukemic cells by bone marrow-derived stromal cells. , 2007, Cancer research.

[29]  Chunaram Choudhary,et al.  Activation mechanisms of STAT5 by oncogenic Flt3-ITD. , 2006, Blood.

[30]  Kyu-Tae Kim,et al.  Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways. , 2006, Blood.

[31]  F. Lee,et al.  YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-kappaB signaling to HIF-1alpha accumulation during hypoxia. , 2007, Oncogene.

[32]  P. Marynen,et al.  The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors. , 2007, Haematologica.

[33]  S. Han,et al.  Hypoxia confers protection against apoptosis via PI3K/Akt and ERK pathways in lung cancer cells. , 2006, Cancer letters.

[34]  J. Dick,et al.  Targeting of CD44 eradicates human acute myeloid leukemic stem cells , 2006, Nature Medicine.

[35]  J. Pouysségur,et al.  Hypoxia signalling in cancer and approaches to enforce tumour regression , 2006, Nature.

[36]  G. Mills,et al.  Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia. , 2006, Cancer research.

[37]  S. Bohlander,et al.  Block of C/EBPα function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations , 2006, The Journal of experimental medicine.

[38]  Steven M Kornblau,et al.  Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. , 2004, Blood.

[39]  C. Thompson,et al.  The survival kinases Akt and Pim as potential pharmacological targets. , 2005, The Journal of clinical investigation.

[40]  N. Sonenberg,et al.  Upstream and downstream of mTOR. , 2004, Genes & development.

[41]  E. Estey,et al.  PML-RARalpha is associated with leptin-receptor induction: the role of mesenchymal stem cell-derived adipocytes in APL cell survival. , 2004, Blood.

[42]  J. Griffin,et al.  The roles of FLT3 in hematopoiesis and leukemia. , 2002, Blood.

[43]  C. Sawyers,et al.  The phosphatidylinositol 3-Kinase–AKT pathway in human cancer , 2002, Nature Reviews Cancer.

[44]  L. del Peso,et al.  Hypoxia Induces the Activation of the Phosphatidylinositol 3-Kinase/Akt Cell Survival Pathway in PC12 Cells , 2001, The Journal of Biological Chemistry.

[45]  A. Giaccia,et al.  Hypoxia activates a platelet-derived growth factor receptor/phosphatidylinositol 3-kinase/Akt pathway that results in glycogen synthase kinase-3 inactivation. , 2001, Cancer research.

[46]  P. Iversen,et al.  Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats , 2000, Cell proliferation.

[47]  G. Mills,et al.  In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[48]  W. Berdel,et al.  Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. , 2000, Blood.

[49]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[50]  E. Ralfkiær,et al.  Changing bone marrow micro‐environment during development of acute myeloid leukaemia in rats , 1998, British journal of haematology.

[51]  H. Kaneko,et al.  Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. , 1996, Leukemia.

[52]  T. Chou,et al.  Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. , 1984, Advances in enzyme regulation.