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Review

Imatinib-resistant chronic myeloid leukemia (CML): Current concepts on pathogenesis and new emerging pharmacologic approaches

Pages 433-448 | Published online: 07 Dec 2022

References

  • AbruzzeseECantonettiMMorinoL2003CNS and cutaneous involvement in patients with chronic myeloid leukemia treated with imatinib in hematologic complete remission: two case reportsJ Clin Oncol214256814615464
  • AbdelhalimABarcosMBlockAW2007Remission of Philadelphia chromosome-positive central nervous system leukemia after dasatinib therapyLeuk Lymphoma481053617487757
  • AgisHMannhalterCSperrWR2004Detection of trisomy 8 in donor-derived Ph- cells in a patient with Ph+ chronic myeloid leukemia successfully treated with Imatinib (STI571) in relapse after allogeneic transplantationLeuk Lymphoma451453815359647
  • AngstreichGRMatsuiWHuffCA2005Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitorsBr J Haematol1303738116042686
  • AichbergerKJHerndlhoferSAgisH2007Liposomal cytarabine for treatment of myeloid central nervous system relapse in chronic myeloid leukemia occurring during imatinib therapyEur J Clin Invest378081317727673
  • AzamMLatekRRDaleyGQ2003Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABLCell1128314312654249
  • BaccaraniMSaglioGGoldmanJ2006Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNetBlood10818092016709930
  • BarbanyGHoglundMSimonssonBSwedish CML Group2002Complete molecular remission in chronic myelogenous leukemia after imatinib therapyN Engl J Med3475394012181416
  • BarnesDJMeloJV2006Primitive, quiescent and difficult to kill: the role of non-proliferating stem cells in chronic myeloid leukemiaCell Cycle52862617172863
  • BartheCGharbiMJLagardeV2002Mutation in the ATP-binding site of BCR-ABL in a patient with chronic myeloid leukaemia with increasing resistance to STI571Br J Haematol1191091112358910
  • BhatiaRHoltzMNiuNPersistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatmentBlood1014701712576334
  • BiernauxCLoosMSelsAHuezGStryckmansP1995Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individualsBlood863118227579406
  • BoltonAEPengBHubertM2004Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjectsCancer Chemother Pharmacol53102614605865
  • BornhäuserMJenkeAFreiberg-RichterJ2004CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluidAnn Hematol83401214673623
  • BoseSDeiningerMGora-TyborJ1998The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual diseaseBlood92336279787174
  • BranfordSRudzkiZWalshS2002High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistanceBlood993472511964322
  • BranfordSRudzkiZWalshS2003Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosisBlood1022768312623848
  • BreedveldPBeijnenJHSchellensJH2006Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugsTrends Pharmacol Sci27172416337012
  • BreedveldPPluimDCiprianiG2005The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patientsCancer Res6525778215805252
  • BrecciaMDiverioDPaneF2006Discontinuation of imatinib therapy after achievement of complete molecular response in a Ph(+) CML patient treated while in long lasting complete cytogenetic remission (CCR) induced by interferonLeuk Res301577916630657
  • BrendelCScharenbergCDohseM2007Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cellsLeukemia 20072112677517519960
  • BurgerHNooterK2004Pharmacokinetic resistance to imatinib mesylate: role of the ABC drug pumps ABCG2 (BCRP) and ABCB1 (MDR1) in the oral bioavailability of imatinibCell Cycle31502515611623
  • BurgerHvan TolHBrokM2005Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumpsCancer Biol Ther47475215970668
  • CalabrettaBPerrottiD2004The biology of CML blast crisisBlood10340102214982876
  • CampbellLJPatsourisCRayerouxKC2002BCR/ABL amplification in chronic myelocytic leukemia blast crisis following imatinib mesylate administrationCancer Genet Cytogenet13930312547154
  • CarterTAWodickaLMShahNP2005Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinasesProc Natl Acad Sci USA10211011616046538
  • CheethamGMCharltonPAGolecJM2007Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680Cancer Lett251323917240048
  • CohenMHWilliamsGJohnsonJR2002Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemiaClin Cancer Res89354212006504
  • CoplandMHamiltonAElrickLJ2006Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fractionBlood1074532916469872
  • CoplandMJorgensenHGHolyoakeTL2005Evolving molecular therapy for chronic myeloid leukaemia – are we on targetHematology103495916203604
  • CortesJKantarjianH2003Advanced-phase chronic myeloid leukemiaSemin Hematol40798612563614
  • CortesJETalpazMGilesF2003Prognostic significance of cytoge-netic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapyBlood101379480012560227
  • CortesJRousselotPKimDW2007Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisisBlood10932071317185463
  • CortesJETalpazMO’BrienS2006Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the World Health Organization proposalCancer10613061516463391
  • Cowan-JacobSWGuezVFendrichG2004Imatinib (STI571) resistance in chronic myelogenous leukemia: molecular basis of the underlying mechanisms and potential strategies for treatmentMini Rev Med Chem42859915032675
  • DaleyGQVan EttenRABaltimoreD1990Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosomeScience247824302406902
  • de KleinAvan KesselAGGrosveldG1982A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemiaNature30076576960256
  • DaiHMarbachPLemaireM2003Distribution of STI-571 to the brain is limited by P-glycoprotein-mediated effluxJ Pharmacol Exp Ther30410859212604685
  • DeiningerMW2007Optimizing therapy of chronic myeloid leukemiaExp Hematol35S11445417379100
  • DevireddyLRGazinCZhuXGreenMR2005A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptakeCell123129330516377569
  • Diaz-BlancoEBrunsINeumannF2007Molecular signature of CD34(+) hematopoietic stem and progenitor cells of patients with CML in chronic phaseLeukemia2149450417252012
  • DrukerBJGuilhotFO’BrienSG2006Five-year follow-up of patients receiving imatinib for chronic myeloid leukemiaN Engl J Med35524081717151364
  • DrukerBJSawyersCLKantarjianH2001Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosomeN Engl J Med34410384211287973
  • DrukerBJTalpazMRestaDJ2001Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemiaN Engl J Med3441031711287972
  • DutcherJPWiernikPH2000Accelerated and blastic phase of chronic myeloid leukemiaCurr Treat Options Oncol1516212057061
  • DutreixCPengBMehringG2004Pharmacokinetic interaction between ketoconazole and imatinib mesylate (Glivec) in healthy subjectsCancer Chemother Pharmacol54290415138710
  • EavesACBarnettMJPonchioLCashmanJDPetzerALEavesCJ1998Differences between normal and CML stem cells: potential targets for clinical exploitationStem Cells16S1778311012149
  • EavesCUdomsakdiCCashmanJ1993The biology of normal and neoplastic stem cells in CMLLeuk Lymphoma11S1245538251904
  • EckelFvon DeliusSMayrM2005Pharmacokinetic and clinical phase II trial of imatinib in patients with impaired liver function and advanced hepatocellular carcinomaOncology693637116319507
  • EistererWJiangXChristO2005Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human diseaseLeukemia194354115674418
  • ElrickLJJorgensenHGMountfordJCHolyoakeTL2005Punish the parent not the progenyBlood1051862615528314
  • FryeRFFitzgeraldSMLagattutaTF2004Effect of St John’s wort on imatinib mesylate pharmacokineticsClin Pharmacol Ther76323915470331
  • GadzickiDvon NeuhoffNSteinemannD2005BCR-ABL gene amplification and overexpression in a patient with chronic myeloid leukemia treated with imatinibCancer Genet Cytogenet159164715899391
  • GargalloPMCuelloMTArangurenPN2003Amplification of the BCR/ABL fusion gene clustered on a masked Philadelphia chromosome in a patient with myeloblastic crisis of chronic myelocytic leukemiaCancer Genet Cytogenet143140412781448
  • GilesFJCortesJEKantarjianHMO’BrienSM2004Accelerated and blastic phases of chronic myelogenous leukemiaHematol Oncol Clin North Am187537415271404
  • GilesFJCortesJJonesD2007MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutationBlood109500216990603
  • GiraltSAAroraMGoldmanJM2007Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemiaBr J Haematol137461717459051
  • GishizkyMLWitteON1992Initiation of deregulated growth of multipotent progenitor cells by bcr-abl in vitroScience25683691375394
  • GoldmanJGordonM2006Why do chronic myelogenous leukemia stem cells survive allogeneic stem cell transplantation or imatinib: does it really matterLeuk Lymphoma471716321820
  • GoldmanJMApperleyJFJonesL1986Bone marrow transplantation for patients with chronic myeloid leukemiaN Engl J Med31420273510388
  • GorreMEMohammedMEllwoodK2001Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplificationScience2938768011423618
  • GrahamSMJorgensenHGAllanE2002Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitroBlood993192511756187
  • GratwohlAHermansJGoldmanJM1998Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow TransplantationLancet3521087929798583
  • GriswoldIJMacPartlinMBummT2006Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinibMol Cell Biol2660829316880519
  • GschwindHPPfaarUWaldmeierFPokornyRSeiberlingMBen-AmMPengBGrossG2005Metabolism and disposition of imatinib mesylate in healthy volunteersDrug Metab Dispos3315031216006570
  • GuilhotFApperleyJKimDW2007Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phaseBlood10941435017264298
  • GumireddyKBakerSJCosenzaSC2005A non-ATP-competitive inhibitor of BCR-ABL overrides imatinib resistanceProc Natl Acad Sci USA1021992715677719
  • HerweijerHSonneveldPBaasFNooterK1990Expression of mdr1 and mdr3 multidrug-resistance genes in human acute and chronic leukemias and association with stimulation of drug accumulation by cyclosporineJ Natl Cancer Inst821133401972761
  • HochhausAErbenPErnstTMuellerMC2007Resistance to targeted therapy in chronic myelogenous leukemiaSemin Hematol44S152417292737
  • HochhausAKantarjianHMBaccaraniM2007Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapyBlood1092303917138817
  • HochhausAKreilSCorbinAS2002Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapyLeukemia162190612399961
  • HolyoakeTLHorrocksCThomasT2000Cell separation improves the sensitivity of detecting rare human normal and leukemic hematopoietic cells in vivo in NOD/SCID miceCytotherapy24112112044221
  • HolyoakeTLJiangXDrummondMW2002Elucidating critical mechanisms of deregulated stem cell turnover in the chronic phase of chronic myeloid leukemiaLeukemia165495811960331
  • HolyoakeTLJiangXJorgensenHG2001Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor-independent growth in vitro in association with up-regulation of expression of interleukin-3Blood97720811157490
  • HooverRRGerlachMJKohEYDaleyGQ2001Cooperative and redundant effects of STAT5 and Ras signaling in BCR/ABL transformed hematopoietic cellsOncogene2058263511593388
  • HughesTPKaedaJBranfordS2003Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemiaN Engl J Med34914233214534335
  • IllmerTSchaichMPlatzbeckerU2004P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylateLeukemia18401814724652
  • JabbourECortesJKantarjianHM2006Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failureBlood1081421316601247
  • JabbourECortesJKantarjianH2007Novel tyrosine kinase inhibitor therapy before allogeneic stem cell transplantation in patients with chronic myeloid leukemia: no evidence for increased transplant-related toxicityCancer1103404417559140
  • JabbourECortesJO’BrienS2007New targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistanceSemin Hematol44S1S253117292738
  • JabbourEKantarjianHMAbruzzoL2007Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phaseBlood
  • JabbourEKantarjianHJonesD2006Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylateLeukemia2017677316855631
  • JiangXSawKMEavesAEavesC2007Instability of BCR-ABL gene in primary and cultured chronic myeloid leukemia stem cellsJ Natl Cancer Inst996809317470736
  • JiangXZhaoYSmithC2007Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapiesLeukemia219263517330101
  • KantarjianHMCortesJO’BrienS2002Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phaseBlood9935475311986206
  • KantarjianHGilesFWunderleL2006Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALLN Engl J Med35425425116775235
  • KantarjianHSawyersCHochhausA2002Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemiaN Engl J Med3466455211870241
  • KantarjianHMTalpazMGilesF2006New insights into the patho-physiology of chronic myeloid leukemia and imatinib resistanceAnn Intern Med1459132317179059
  • KantarjianHMTalpazMO’BrienS2003Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemiaBlood101473512393385
  • KhorashadJSAnandMMarinD2006The presence of a BCR-ABL mutant allele in CML does not always explain clinical resistance to imatinibLeukemia206586316467863
  • KimHJJungCWKimK2006Isolated blast crisis in CNS in a patient with chronic myelogenous leukaemia maintaining major cytogenetic response after imatinibJ Clin Oncol2440282916921058
  • KimuraSNaitoHSegawaH2005NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemiaBlood10639485416105974
  • KreuzerKALe CoutrePLandtO2003Preexistence and evolution of imatinib mesylate-resistant clones in chronic myelogenous leukemia detected by a PNA-based PCR clamping techniqueAnn Hematol82284912692682
  • le CoutrePKreuzerKAPurscheS2004Pharmacokinetics and cellular uptake of imatinib and its main metabolite CGP74588Cancer Chemother Pharmacol533132314658008
  • le CoutrePTassiEVarella-GarciaM2000Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplificationBlood9517586610688835
  • LeisJFStepanDECurtinPT2004Central nervous system failure in patients with chronic myelogenous leukemia lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic leukemia treated with imatinib (STI-571)Leuk Lymphoma45695815160941
  • LiZQiaoYLiuB2005Combination of imatinib mesylate with autologous leukocyte-derived heat shock protein and chronic myelogenous leukemiaClin Cancer Res114460815958631
  • LinHMonacoGSunT2005Bcr-Abl-mediated suppression of normal hematopoiesis in leukemiaOncogene2432465615735695
  • LinYBruyereHHorsmanDE2006Philadelphia-negative clonal hematopoiesis following imatinib therapy in patients with chronic myeloid leukemia: a report of nine cases and analysis of predictive factorsCancer Genet Cytogenet170162316965950
  • LoriauxMDeiningerM2004Clonal cytogenetic abnormalities in Philadelphia chromosome negative cells in chronic myeloid leukemia patients treated with imatinibLeuk Lymphoma45219720315512807
  • LugoTGPendergastAMMullerAJWitteON1990Tyrosine kinase activity and transformation potency of bcr-abl oncogene productsScience2471079822408149
  • MahonFXBellocFLagardeV2003MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line modelsBlood10123687312609962
  • MarktelSMarinDFootN2003Chronic myeloid leukemia in chronic phase responding to imatinib: the occurrence of additional cytogenetic abnormalities predicts disease progressionHaematologica88260712651263
  • MartinelliGSoveriniSRostiG2005New tyrosine kinase inhibitors in chronic myeloid leukemiaHaematologica905344115820950
  • MatsudaMMoritaYShimadaT2005Extramedullary blast crisis derived from 2 different clones in the central nervous system and neck during complete cytogenetic remission of chronic myelogenous leukemia treated with imatinib mesylateInt J Hematol81307915914360
  • MedinaJKantarjianHTalpazM2003Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phaseCancer9819051114584073
  • MeloJVBarnesDJ2007Chronic myeloid leukaemia as a model of disease evolution in human cancerNat Rev Cancer74415317522713
  • MeloJVDeiningerMW2004Biology of chronic myelogenous leukemia – signaling pathways of initiation and transformationHematol Oncol Clin North Am185456815271392
  • MenzelHvon BubnoffNHochhausA2007Successful allogeneic stem cell transplantation in second chronic-phase CML induced by the tyrosine kinase inhibitor nilotinib (AMN107) after blast crisis under imatinibBone Marrow Transplant4083417450179
  • MichorFHughesTPIwasaY2005Dynamics of chronic myeloid leukaemiaNature43512677015988530
  • MorelFBrisMJHerryA2003Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinibEur J Haematol70235912656747
  • NavarroJTFeliuEGrauJ2007Monosomy 7 with severe myelodysplasia developing during imatinib treatment of Philadelphia-positive chronic myeloid leukemia: Two cases with a different outcomeAm J Hematol828495117563075
  • NevianiPSanthanamRTrottaR2006The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET proteinCancer Cell535568
  • Nguyen KhacFWaillMCRomanaSP2002Identical abnormality of the short arm of chromosome 18 in two Philadelphia-positive chronic myelocytic leukemia patients with erythroblastic transformation, resulting in duplication of BCR-ABL1 fusionCancer Genet Cytogenet13822612419580
  • NicoliniFECormSLeQH2006Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP)Leukemia201061616642048
  • NowellPCHungerfordDA1960A minute chromosome in human granulocytic leukemiaScience1321497
  • O’BrienSGGuilhotFLarsonRA2003Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemiaN Engl J Med348994100412637609
  • O’BrienSGMeinhardtPBondE2003Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemiaBr J Cancer891855914612892
  • O’DwyerMEMauroMJBlasdelC2004Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylateBlood103451514512312
  • O’HareTWaltersDKStoffregenEPJiaTManleyPWMestanJCowan-JacobSWLeeFYHeinrichMCDeiningerMWDrukerBJ2005In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutantsCancer Res654500515930265
  • PappasPKaravasilisVBriasoulisE2005Pharmacokinetics of imatinib mesylate in end stage renal disease. A case studyCancer Chemother Pharmacol563586015883819
  • PavluJCzepulkowskiBKaczmarskiRJan-MohamedR2005Early blastic transformation with CNS infiltration in a patient with chronic myeloid leukaemia treated with imatinibLancet Oncol612815683824
  • PendergastAMQuilliamLACripeLD1993BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor proteinCell75175858402896
  • PengBDutreixCMehringG2004Absolute bioavailability of imatinib (Glivec) orally versus intravenous infusionJ Clin Pharmacol441586214747424
  • PengBHayesMRestaD2004Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patientsJ Clin Oncol229354214990650
  • PengCBrainJHuY2007Inhibition of heat shock protein 90 prolongs survival of mice with BCR-ABL-T315I-induced leukemia and suppresses leukemic stem cellsBlood1106788517395781
  • PengBLloydPSchranH2005Clinical pharmacokinetics of imatinibClin Pharmacokinet448799416122278
  • PicardSTitierKEtienneG2007Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemiaBlood1093496917192396
  • Pienkowska-GrelaBWoronieckaRSolarskaI2007Complete cytogenetic and molecular response after imatinib treatment for chronic myeloid leukemia in a patient with atypical karyotype and BCR-ABL b2a3 transcriptCancer Genet Cytogenet174111517452251
  • PuilLLiuJGishG1994Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathwayEMBO J13764738112292
  • Quintas-CardamaAKantarjianHJonesD2007Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failureBlood109497916990591
  • RadichJPDaiHMaoM2006Gene expression changes associated with progression and response in chronic myeloid leukemiaProc Natl Acad Sci USA1032794916477019
  • RahmaniMNguyenTKDentP2007The multikinase inhibitor sorafenib induces apoptosis in highly imatinib mesylate-resistant BCR/ABL+ human leukemia cells in association with STAT5 inhibition and MCL-1 downregulationMol Pharmacol727889517595328
  • RajappaSUppinSGRaghunadharaoD2004Isolated central nervous system blast crisis in chronic myeloid leukaemiaHematol Oncol221798115995975
  • RenR2005Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemiaNat Rev Cancer51728315719031
  • Roche-LestienneCPreudhommeC2003Mutations in the ABL kinase domain pre-exist the onset of imatinib treatmentSemin Hematol40S280212783380
  • Roche-LestienneCSoenen-CornuVGrardel-DuflosN2002Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatmentBlood1001014812130516
  • RoederIHornMGlaucheIHochhausAMuellerMCLoefflerM2006Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implicationsNat Med121181417013383
  • RoumiantsevSShahNPGorreME2002Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loopProc Natl Acad Sci USA9910700512149456
  • RousselotPHuguetFReaD2007Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 yearsBlood109586016973963
  • RowleyJD1973A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa stainingNature24329034126434
  • RyttingMEWierdaWG2004Central nervous system relapse in two patients with chronic myelogenous leukemia in myeloid blastic phase on imatinib mesylate therapyLeuk Lymphoma451623615370215
  • SattlerMGriffinJD2003Molecular mechanisms of transformation by the BCR-ABL oncogeneSemin Hematol4041012783368
  • SawyersCLHochhausAFeldmanE2002Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II studyBlood993530911986204
  • SeniorK2003Gleevec does not cross blood-brain barrierLancet Oncol419812681250
  • ShahNPNicollJMNagarB2002Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemiaCancer Cell21172512204532
  • ShahNPTranCLeeFY2004Overriding imatinib resistance with a novel ABL kinase inhibitorScience30539940115256671
  • ShetASJahagirdarBNVerfaillieCM2002Chronic myelogenous leukemia: mechanisms underlying disease progressionLeukemia1614021112145676
  • SilbermanGCrosseMGPetersonEA1994Availability and appropriateness of allogeneic bone marrow transplantation for chronic myeloid leukemia in 10 countriesN Engl J Med331106378090167
  • SillaberCGesbertFFrankDA2000STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cellsBlood9521182510706883
  • SkaggsBJGorreMERyvkinA2006Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutantsProc Natl Acad Sci USA103194667117164333
  • SkorskiTBellacosaANieborowska-SkorskaM1997Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathwayEMBO J166151619321394
  • SoveriniSMartinelliGRostiG2005ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid LeukemiaJ Clin Oncol234100915867198
  • TakayamaNSatoNO’BrienSG2002Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluidBr J Haematol119106812358909
  • TalpazMShahNPKantarjianH2006Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemiasN Engl J Med35425314116775234
  • TalpazMSilverRTDrukerBJ2002Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 studyBlood9919283711877262
  • TanakaKArifMKyoT2000Transposition of duplicated chromosomal segment involving fused BCR-ABL gene or ABL oncogene alone in chronic myelocytic leukemia and Ph chromosome-positive acute leukemia with complex karyotypesCancer Genet Cytogenet11981410812164
  • TauchiTOhyashikiK2006The second generation of BCR-ABL tyrosine kinase inhibitorsInt J Hematol8329430016757427
  • TerreCEclacheVRousselotP2004Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemiaLeukemia181340615190256
  • ThomasJWangLClarkREPirmohamedM2004Active transport of imatinib into and out of cells: implications for drug resistanceBlood10437394515315971
  • TsengPHLinHPZhuJ2005Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistanceBlood1054021715665113
  • Van EttenRA2007Oncogenic signaling: new insights and controversies from chronic myeloid leukemiaJ Exp Med204461517353369
  • VerbeekWKonigHBoehmJ2006Continuous complete hematological and cytogenetic remission with molecular minimal residual disease 9 years after discontinuation of interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemiaActa Haematol1151091216424660
  • VilluendasRSteegmannJLPollanM2006Identification of genes involved in imatinib resistance in CML: a gene-expression profiling approachLeukemia2010475416598311
  • VolpeGCignettiAPanuzzoC2007Alternative BCR/ABL splice variants in Philadelphia chromosome-positive leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approachesCancer Res675300717545610
  • von BubnoffNSchnellerFPeschelC2002BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective studyLancet3594879111853795
  • WangLGiannoudisALaneS2007Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemiaClin Pharmacol Ther10.1038/sj.clpt.6100268
  • WeisbergEManleyPWBreitensteinW2005Characterization of AMN107, a selective inhibitor of native and mutant Bcr-AblCancer Cell71294115710326
  • WeisbergEManleyPMestanJ2006AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABLBr J Cancer941765916721371
  • WeisbergECatleyLWrightRD2007Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemiasBlood10921122017068153
  • WeisbergEGriffinJD2000Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABL-transformed hematopoietic cell linesBlood95349850510828035
  • WeisbergEManleyPWCowan-JacobSW2007Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemiaNat Rev Cancer73455617457302
  • WeisserMSchleuningMHaferlachC2007Allogeneic stem-cell transplantation provides excellent results in advanced stage chronic myeloid leukemia with major cytogenetic response to pre-transplant imatinib therapyLeuk Lymphoma4829530117325889
  • WestermannJKoppJvan LessenA2007Vaccination with autologous non-irradiated dendritic cells in patients with bcr/abl+ chronic myeloid leukaemiaBr J Haematol13729730617408402
  • WetzlerMTalpazMVan EttenRA1993Subcellular localization of Bcr, Abl, and Bcr-Abl proteins in normal and leukemic cells and correlation of expression with myeloid differentiationJ Clin Invest921925398408645
  • WhiteDLSaundersVAQuinnSR2007Imatinib increases the intracellular concentration of nilotinib, which may explain the observed synergy between these drugsBlood10936091017409347
  • WildRCastanedaSFleflehC2004BMS-354825, a dual SRC/ABL kinase inhibitor, displays potent anti-tumor activity in a model of intracranial CML growthBlood104549a
  • WolffNCRichardsonJAEgorinMIlariaRL2003The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate for Bcr/Abl-induced leukemiaBlood1015010312595307
  • YokotaAKimuraSMasudaS2007INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activityBlood1093061416954504
  • ZhengCLiLHaakM2006Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisisLeukemia2010283416617318

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