PIM and AKT kinase inhibitors show synergistic cytotoxicity in acute myeloid leukaemia that is associated with convergence on mTOR and MCL1 pathways

scientific article

PIM and AKT kinase inhibitors show synergistic cytotoxicity in acute myeloid leukaemia that is associated with convergence on mTOR and MCL1 pathways is …
instance of (P31):
scholarly articleQ13442814

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P356DOI10.1111/BJH.13013
P698PubMed publication ID24975213

P50authorRosemary GaleQ59828924
David C LinchQ89467453
P2093author name stringChloe Stengel
Dennis Huszar
Barry R Davies
Asim Khwaja
Koremu Meja
Rob Sellar
P2860cites workmTOR signaling in growth control and diseaseQ24634174
Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinasesQ27681337
Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic backgroundQ27851716
The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell deathQ28204906
PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cellsQ28237807
Targeting the phosphoinositide 3-kinase pathway in cancerQ29615809
Drug combination studies and their synergy quantification using the Chou-Talalay methodQ29617422
Tumour heterogeneity and cancer cell plasticityQ29617990
Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia.Q33882849
Modeling pO(2) distributions in the bone marrow hematopoietic compartment. I. Krogh's modelQ34176018
Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemiaQ35125923
Delving deeper: MCL-1's contributions to normal and cancer biologyQ36494824
Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemiaQ37226744
AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemiaQ37564783
For better or for worse: the role of Pim oncogenes in tumorigenesisQ37820056
The PIM family of serine/threonine kinases in cancerQ38098139
Pim2 is required for maintaining multiple myeloma cell growth through modulating TSC2 phosphorylationQ38266874
Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutationsQ38360085
Optimal induction of myeloma cell death requires dual blockade of phosphoinositide 3-kinase and mTOR signalling and is determined by translocation subtypeQ39380262
Pim-1 plays a pivotal role in hypoxia-induced chemoresistance.Q39844632
Activating alleles of JAK3 in acute megakaryoblastic leukemiaQ40255542
JAK2 V617F tyrosine kinase mutation in cell lines derived from myeloproliferative disordersQ40330808
Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survivalQ40501190
Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemiasQ40615155
Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survivalQ41868647
Selectively targeting Mcl-1 for the treatment of acute myelogenous leukemia and solid tumorsQ41907705
Potential use of selective and nonselective Pim kinase inhibitors for cancer therapyQ42716236
Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper siteQ44997396
Murine leukemia virus-induced T-cell lymphomagenesis: Integration of proviruses in a distinct chromosomal regionQ45796591
Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumorsQ45846353
The FLT3 and Pim kinases inhibitor SGI-1776 preferentially target FLT3-ITD AML cells.Q50502283
Hypoxia-inducible proto-oncogene Pim-1 is a prognostic marker in pancreatic ductal adenocarcinomaQ57767618
P433issue1
P407language of work or nameEnglishQ1860
P921main subjectleukemiaQ29496
cytotoxicityQ246181
P304page(s)69-79
P577publication date2014-06-30
P1433published inBritish Journal of HaematologyQ4970200
P1476titlePIM and AKT kinase inhibitors show synergistic cytotoxicity in acute myeloid leukaemia that is associated with convergence on mTOR and MCL1 pathways
P478volume167

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cites work (P2860)
Q38798340Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma
Q38803880Elevated PIM2 gene expression is associated with poor survival of patients with acute myeloid leukemia.
Q38892684FLT3-ITD confers resistance to the PI3K/Akt pathway inhibitors by protecting the mTOR/4EBP1/Mcl-1 pathway through STAT5 activation in acute myeloid leukemia
Q52366350FLT3-ITD induces expression of Pim kinases through STAT5 to confer resistance to the PI3K/Akt pathway inhibitors on leukemic cells by enhancing the mTORC1/Mcl-1 pathway.
Q39326047Inhibition of mTOR kinase as a therapeutic target for acute myeloid leukemia
Q37437166Intrinsic resistance to PIM kinase inhibition in AML through p38α-mediated feedback activation of mTOR signaling
Q92545473Isoferulic acid inhibits human leukemia cell growth through induction of G2/M‑phase arrest and inhibition of Akt/mTOR signaling
Q41190391Novel inhibition of PIM2 kinase has significant anti-tumor efficacy in multiple myeloma
Q52846906Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer.
Q38370023PIM kinase (and Akt) biology and signaling in tumors.
Q64100912PIM kinase inhibitor, AZD1208, inhibits protein translation and induces autophagy in primary chronic lymphocytic leukemia cells
Q54976784Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells.
Q39716970Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2α Kinase Levels in NRAS(Q61) Mutant Cells.
Q90240397Phosphorylation of DEPDC5, a component of the GATOR1 complex, releases inhibition of mTORC1 and promotes tumor growth
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Q89637594Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer
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Q36545566The PIM inhibitor AZD1208 synergizes with ruxolitinib to induce apoptosis of ruxolitinib sensitive and resistant JAK2-V617F-driven cells and inhibit colony formation of primary MPN cells
Q92052566The first-in-human study of the pan-PIM kinase inhibitor PIM447 in patients with relapsed and/or refractory multiple myeloma
Q38262117The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression

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