Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment.

scientific article

Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment. is …
instance of (P31):
scholarly articleQ13442814
review articleQ7318358

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P356DOI10.18632/ONCOTARGET.477
P932PMC publication ID3380573
P698PubMed publication ID22564882
P5875ResearchGate publication ID224917330

P50authorFrancesca BuontempoQ57070544
Camilla EvangelistiQ57233682
P2093author name stringJames A McCubrey
Alberto M Martelli
Milena Fini
Daniela Bressanin
Francesca Chiarini
Alessandra Cappellini
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Intracellular reactive oxygen species are essential for PI3K/Akt/mTOR-dependent IL-7-mediated viability of T-cell acute lymphoblastic leukemia cellsQ43599325
Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteinsQ44117862
Possible dominant-negative mutation of the SHIP gene in acute myeloid leukemiaQ44279382
Survival of acute myeloid leukemia cells requires PI3 kinase activationQ44408364
Genetic variegation of clonal architecture and propagating cells in leukaemiaQ44426152
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Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemiaQ44536202
Bcr-Abl kinase modulates the translation regulators ribosomal protein S6 and 4E-BP1 in chronic myelogenous leukemia cells via the mammalian target of rapamycinQ44605109
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Identification of a small subpopulation of candidate leukemia-initiating cells in the side population of patients with acute myeloid leukemiaQ83030425
A selective inhibitor of the p110delta isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16Q83350735
Microarray detection of multiple recurring submicroscopic chromosomal aberrations in pediatric T-cell acute lymphoblastic leukemiaQ83557743
Single cell analysis of phosphoinositide 3-kinase/Akt and ERK activation in acute myeloid leukemia by flow cytometryQ83977171
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Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reactionQ28378871
A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)Q28640016
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Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa stainingQ29614339
Molecular mechanisms of mTOR-mediated translational controlQ29615529
Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cellsQ29616552
Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancerQ29618030
Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activityQ29618117
Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivoQ29619355
Intrinsic regulation of the interactions between the SH3 domain of p85 subunit of phosphatidylinositol-3 kinase and the protein network of BCR/ABL oncogenic tyrosine kinaseQ30160114
The proto-oncogene product p120CBL and the adaptor proteins CRKL and c-CRK link c-ABL, p190BCR/ABL and p210BCR/ABL to the phosphatidylinositol-3' kinase pathway.Q30177048
Association of phosphatidylinositol 3-kinase with SHC in chronic myelogeneous leukemia cells.Q30193531
A phase 2 clinical trial of deforolimus (AP23573, MK-8669), a novel mammalian target of rapamycin inhibitor, in patients with relapsed or refractory hematologic malignanciesQ33379469
Targeting the PI3K/AKT/mTOR signaling network in acute myelogenous leukemiaQ33493174
Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitorQ33597663
PTEN is a tumor suppressor in CML stem cells and BCR-ABL-induced leukemias in miceQ33608760
Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000).Q33645760
Acute T-cell leukemias remain dependent on Notch signaling despite PTEN and INK4A/ARF loss.Q33677433
Autocrine IGF-1/IGF-1R signaling is responsible for constitutive PI3K/Akt activation in acute myeloid leukemia: therapeutic value of neutralizing anti-IGF-1R antibodyQ33707416
Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(-) fractionQ33722630
Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formationQ33732463
Acute myeloid leukemiaQ33741270
Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistanceQ33755338
The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients.Q34024558
Arsenic trioxide - An old drug rediscoveredQ34054167
Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's MacroglobulinemiaQ34164289
Targeting the translational apparatus to improve leukemia therapy: roles of the PI3K/PTEN/Akt/mTOR pathwayQ34173253
The phosphoinositide 3-kinase/AKT1 pathway involvement in drug and all-trans-retinoic acid resistance of leukemia cellsQ34173746
INPP4B: the new kid on the PI3K blockQ34177821
Functional proteomic profiling of AML predicts response and survivalQ34184598
PTEN Tumor Suppressor Network in PI3K-Akt Pathway ControlQ34202681
Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemiaQ34213539
Rapamycin sensitizes T-ALL cells to dexamethasone-induced apoptosis.Q34387833
Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect that is modulated by IL-7-mediated signalingQ34391120
Suppression of leukemia development caused by PTEN lossQ34533833
Personalized Medicine: Marking a New Epoch in Cancer Patient ManagementQ37778667
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Modern therapy of acute lymphoblastic leukemiaQ37827276
Leukemia stem cells and microenvironment: biology and therapeutic targetingQ37827279
Therapeutic advances in acute myeloid leukemiaQ37827282
Regulation of mammalian target of rapamycin and mitogen activated protein kinase pathways by BCR-ABL.Q37836931
The biological and therapeutic relevance of mRNA translation in cancerQ37848652
Targeting translation dependence in cancerQ37850227
The cancer stem cell: premises, promises and challengesQ37851011
Gene expression profiling in MDS and AML: potential and future avenues.Q37858877
Philadelphia chromosome-positive acute lymphoblastic leukemia: current treatment and future perspectivesQ37862648
Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy.Q37865381
Autophagy as a target for anticancer therapyQ37876679
Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in cancer stem cellsQ37886012
Cytokines and microRNA in pediatric B-acute lymphoblastic leukemiaQ37901917
Notch in T-ALL: new players in a complex disease.Q37903126
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Cancer stem cells in tumor heterogeneity.Q37933902
AMPK and mTOR in cellular energy homeostasis and drug targetsQ37948152
The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia.Q37953891
AMPK in BCR-ABL expressing leukemias. Regulatory effects and therapeutic implicationsQ37976243
Autocrine pathway of angiopoietins-Tie2 system in AML cells: association with phosphatidyl-inositol 3 kinaseQ38338053
The dual kinase inhibitor NVP-BEZ235 in combination with cytotoxic drugs exerts anti-proliferative activity towards acute lymphoblastic leukemia cells.Q39404545
Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B.Q39414084
Silencing of ETV6/RUNX1 abrogates PI3K/AKT/mTOR signaling and impairs reconstitution of leukemia in xenografts.Q39441263
Arsenic disulfide synergizes with the phosphoinositide 3-kinase inhibitor PI-103 to eradicate acute myeloid leukemia stem cells by inducing differentiationQ39497826
PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activityQ39507948
Levels of p27 sensitize to dual PI3K/mTOR inhibitionQ39529578
Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia.Q39590044
Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitorQ39591379
Inhibition of PI3K/mTOR pathways in glioblastoma and implications for combination therapy with temozolomideQ39593159
BCR-ABL1-independent PI3Kinase activation causing imatinib-resistanceQ39596672
Targeting of active mTOR inhibits primary leukemia T cells and synergizes with cytotoxic drugs and signaling inhibitorsQ39600915
CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viabilityQ39642145
The mammalian target of rapamycin inhibitor RAD001 (everolimus) synergizes with chemotherapeutic agents, ionizing radiation and proteasome inhibitors in pre-B acute lymphocytic leukemiaQ39643259
Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia.Q39650704
Crosstalk between the PI3K/mTOR and MEK/ERK pathways involved in the maintenance of self-renewal and tumorigenicity of glioblastoma stem-like cells.Q39653276
WJD008, a dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin inhibitor, prevents PI3K signaling and inhibits the proliferation of transformed cells with oncogenic PI3K mutantQ39696876
Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitorQ39718159
Compensatory activation of Akt in response to mTOR and Raf inhibitors - a rationale for dual-targeted therapy approaches in neuroendocrine tumor diseaseQ39720433
NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growthQ34582832
The two TORCs and Akt.Q34617423
Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 studyQ34627586
Normalizing a hyperactive mTOR initiates muscle growth during obesityQ34852371
The role of phosphatidylinositol 3-kinase-δ in the immunomodulatory effects of lenalidomide in chronic lymphocytic leukemiaQ34923824
PI3K and mTOR inhibitors: a new generation of targeted anticancer agentsQ34939865
Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and agingQ34966603
Gain-of-function mutations in interleukin-7 receptor-α (IL7R) in childhood acute lymphoblastic leukemiasQ34973772
PKB binding proteins. Getting in on the Akt.Q34990565
Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984-2001: a report from the children's oncology groupQ34992080
Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapseQ35102275
The role of SHIP in cytokine-induced signalingQ35106192
Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia.Q35144582
Role of Pten in leukemia stem cellsQ35169570
High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signalingQ35208383
PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axisQ35217174
Low expression of PP2A regulatory subunit B55α is associated with T308 phosphorylation of AKT and shorter complete remission duration in acute myeloid leukemia patientsQ35316765
High VLA-4 expression is associated with adverse outcome and distinct gene expression changes in childhood B-cell precursor acute lymphoblastic leukemia at first relapseQ35528643
Targeting the PI3K/Akt/mTOR pathway--beyond rapalogsQ35640098
Involvement of Akt-1 and mTOR in sensitivity of breast cancer to targeted therapyQ35640228
Elevated PI3K signaling drives multiple breast cancer subtypesQ35640263
Chronic myeloid leukemia stem cells in the era of targeted therapies: resistance, persistence and long-term dormancy.Q35640320
Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007.Q35651744
Selective targeting of the mTORC1/2 protein kinase complexes leads to antileukemic effects in vitro and in vivo.Q35664310
Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human healthQ35679353
Targets and mechanisms for the regulation of translation in malignant transformationQ35750114
Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.Q35751042
Will PI3K pathway inhibitors be effective as single agents in patients with cancer?Q35764392
Advances in protein kinase B signalling: AKTion on multiple frontsQ35766370
mTOR regulates cell survival after etoposide treatment in primary AML cellsQ35848196
The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALLQ35850028
FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemiaQ35945171
Concise review: Emerging concepts in clinical targeting of cancer stem cellsQ35971159
Detection of serine 473 phosphorylated Akt in acute myeloid leukaemia blasts by flow cytometryQ45029000
Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficienciesQ45067792
Antileukemic activity of rapamycin in acute myeloid leukemia.Q45154681
PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kappaB, Mapkinase and p53 pathwaysQ45259661
Protein synthesis is resistant to rapamycin and constitutes a promising therapeutic target in acute myeloid leukemia.Q46003222
Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors.Q46047974
Blockade of mTOR signaling potentiates the ability of histone deacetylase inhibitor to induce growth arrest and differentiation of acute myelogenous leukemia cellsQ46375225
Rapamycin stimulates apoptosis of childhood acute lymphoblastic leukemia cellsQ46477311
Leukemia stem cellsQ46509360
PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML.Q46544691
The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML.Q46544703
Targeting PI3K/mTOR signaling in cancerQ46617891
NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951.Q47259599
Wilms tumor 1 (WT1) gene mutations in pediatric T-cell malignancies.Q47268104
ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemiaQ47290417
The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotypeQ48059777
Nutrient sensing in the mTOR/S6K1 signalling pathwayQ48235664
The eukaryotic initiating factor 4E protein is overexpressed, but its level has no prognostic impact in acute myeloid leukaemia.Q50510141
Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia.Q50649768
Interaction of interleukin-7 and interleukin-3 with the CXCL12-induced proliferation of B-cell progenitor acute lymphoblastic leukemia.Q51008910
Stem cell gene expression programs influence clinical outcome in human leukemia.Q51856192
Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells.Q51890946
Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit glucocorticoid resistance.Q51900663
Activation of integrin-linked kinase is a critical prosurvival pathway induced in leukemic cells by bone marrow-derived stromal cells.Q52576345
Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000.Q52906689
PP2A impaired activity is a common event in acute myeloid leukemia and its activation by forskolin has a potent anti-leukemic effect.Q53275436
Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients.Q53334759
Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways.Q53526869
Chemotherapy resistance in acute lymphoblastic leukemia requires hERG1 channels and is overcome by hERG1 blockers.Q54635631
Identification of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of adult T-cell leukemia/lymphoma.Q55239327
Acute lymphoblastic leukaemiaQ56722375
The Akt/mammalian target of rapamycin signal transduction pathway is activated in high-risk myelodysplastic syndromes and influences cell survival and proliferationQ56995267
The insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 induces apoptosis in acute myeloid leukemia cells exhibiting autocrine insulin-like growth factor-I secretionQ56995355
Essential role for the p110 isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemiaQ57220263
Bone marrow stromal cells and the upregulation of interleukin-8 production in human T-cell acute lymphoblastic leukemia through the CXCL12/CXCR4 axis and the NF- B and JNK/AP-1 pathwaysQ57425916
GAB2 is a novel target of 11q amplification in AML/MDSQ58957431
PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia preventionQ59067116
Tumor growth need not be driven by rare cancer stem cellsQ59606871
CD34+ cells from AML with mutated NPM1 harbor cytoplasmic mutated nucleophosmin and generate leukemia in immunocompromised miceQ60171380
Negative prognostic impact of PTEN mutation in pediatric T-cell acute lymphoblastic leukemiaQ61774820
Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populationsQ62658217
Phosphatase and tensin homologue phosphorylation in the C-terminal regulatory domain is frequently observed in acute myeloid leukaemia and associated with poor clinical outcomeQ73701961
Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemiaQ79143621
Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche deQ79527735
Implication of RICTOR in the mTOR inhibitor-mediated induction of insulin-like growth factor-I receptor (IGF-IR) and human epidermal growth factor receptor-2 (Her2) expression in gastrointestinal cancer cellsQ39746076
The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells.Q39790449
Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia.Q39832054
RAD001 (Everolimus) induces autophagy in acute lymphoblastic leukemiaQ39861488
SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia.Q39921977
AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B.Q39932311
PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viabilityQ39933367
Hypersensitivity of Ph-positive lymphoid cell lines to rapamycin: Possible clinical application of mTOR inhibitorQ39941278
A critical role for Lyn in acute myeloid leukemia.Q40040911
Eradicating cancer cells: struggle with a chameleonQ40047489
Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38.Q40054340
Autocrine insulin-like growth factor-I signaling promotes growth and survival of human acute myeloid leukemia cells via the phosphoinositide 3-kinase/Akt pathwayQ40117414
Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases.Q40118489
Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemiaQ40158237
Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistanceQ40225720
A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in gliomaQ40280414
The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET proteinQ40351786
Activation of mammalian target of rapamycin in transformed B lymphocytes is nutrient dependent but independent of Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, insulin growth factor-I, and serum.Q40377835
Phosphoinositide 3-kinase/Akt inhibition increases arsenic trioxide-induced apoptosis of acute promyelocytic and T-cell leukaemiasQ40382560
Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemiaQ40400934
Differential regulation of the p70 S6 kinase pathway by interferon alpha (IFNalpha) and imatinib mesylate (STI571) in chronic myelogenous leukemia cellsQ40435523
Phosphoinositide 3-kinase/Akt involvement in arsenic trioxide resistance of human leukemia cellsQ40488705
Inhibition of PI3K, mTOR and MEK signaling pathways promotes rapid apoptosis in B-lineage ALL in the presence of stromal cell support.Q40501536
Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen speciesQ40503994
Inhibition of phosphatidylinositol 3'-kinase induces preferentially killing of PTEN-null T leukemias through AKT pathway.Q40538322
Vascular endothelial growth factor receptor-1 and receptor-2 initiate a phosphatidylinositide 3-kinase-dependent clonogenic response in acute myeloid leukemia cellsQ40548220
Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemiasQ40615155
P275copyright licenseCreative Commons Attribution 2.5 GenericQ18810333
P433issue4
P407language of work or nameEnglishQ1860
P921main subjectacute leukemiaQ976388
mechanism of actionQ3271540
phosphoinositide-3 kinase inhibitorQ7187512
enzymeQ8047
leukemiaQ29496
Serine/threonine-protein kinase TORQ24723029
sirolimusQ32089
P5008on focus list of Wikimedia projectScienceSourceQ55439927
P304page(s)371-394
P577publication date2012-04-01
P1433published inOncotargetQ1573155
P1476titleTwo hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment
P478volume3

Reverse relations

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