Chapter 11
Strategies to Overcome Drug Resistance in Acute and Chronic Leukemias
Eric Solary,
Vincent Ribrag,
Stéphane de Botton,
Eric Solary
Inserm UMR866, Dijon, France
University of Burgundy, Faculty of Medicine, Dijon, France
Institut Gustave Roussy, Inserm UMRU790, Villejuif, France
Search for more papers by this authorVincent Ribrag
Institut Gustave Roussy, Inserm UMRU790, Villejuif, France
Clinical Hematology Unit, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorStéphane de Botton
Institut Gustave Roussy, Inserm UMRU790, Villejuif, France
Clinical Hematology Unit, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorEric Solary,
Vincent Ribrag,
Stéphane de Botton,
Eric Solary
Inserm UMR866, Dijon, France
University of Burgundy, Faculty of Medicine, Dijon, France
Institut Gustave Roussy, Inserm UMRU790, Villejuif, France
Search for more papers by this authorVincent Ribrag
Institut Gustave Roussy, Inserm UMRU790, Villejuif, France
Clinical Hematology Unit, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorStéphane de Botton
Institut Gustave Roussy, Inserm UMRU790, Villejuif, France
Clinical Hematology Unit, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorBook Editor(s):Ahcène Boumendjel, Jean Boutonnat,
Jacques Robert,
Jean Boutonnat
Institut Jean Roget, Université Joseph Fourier, Grenoble, France
Hôpital Michallon de Grenoble, Grenoble, France
Search for more papers by this authorJacques Robert
Institut Bergonié, Université Victor Segalen, Bordeaux, France
Search for more papers by this authorFirst published: 15 June 2009
Series Editor(s): Binghe Wang,
Binghe Wang
Search for more papers by this authorSummary
This chapter contains sections titled:
-
Introduction
-
MDR
-
Resistance to specific drugs
-
Conclusions
-
References
REFERENCES
- Kartner N, Riordan JR, and Ling V. 1983. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cells. Science 221: 1285–1288.
- Juliano RL and Ling V. 1976. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455: 152–162.
- Pirker R, Wallner J, Geissler K et al. 1991. MDR1 gene expression and treatment outcome in acute myeloid leukemia. J Natl Cancer Inst 83: 708–712.
- Nikles D and Tampé R. 2007. Targeted degradation of ABC transporters in health and disease. J Bioenerg Biomembr 39: 489–497.
- Pallis M, Turzanski J, Higashi Y, and Russell N. 2002. P-glycoprotein in acute myeloid leukaemia: Therapeutic implications of its association with both a multidrug-resistant and an apoptosis-resistant phenotype. Leuk Lymphoma 43: 1221–1228.
- Johnstone RW, Cretney E, and Smyth MJ. 1999. P-glycoprotein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death. Blood 93: 1075–1085.
- Smyth MJ, Krasovskis E, Sutton VR, and Johnstone RW. 1998. The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis. Proc Natl Acad Sci U S A 95: 7024–7029.
- Beck WT, Grogan TM, Willman CL, Cordon-Cardo C, Parham DM, and Kuttesch JF. 1996. Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: Consensus recommendations. Cancer Res 56: 3010–3020.
- Campos L, Guyotat D, Archimbaud E, Calmard-Oriol P, Tsuruo T, Troncy J et al. 1992. Clinical significance of multidrug resistance P-glycoprotein expression in acute nonlymphoblastic leukemia cells at diagnosis. Blood 79: 473–476.
- Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, Chen IM et al. 1997. Acute myeloid leukemia in the elderly: Assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group Study. Blood 89: 3323–3329.
- Samdani A, Vijapurkar U, Grimm MA, Spier CS, Grogan TM, Glinsmann-Gibson BJ et al. 1996. Cytogenetics and P-glycoprotein (P-gp) are independent predictors of treatment outcome in acute myeloid leukemia (AML). Leuk Res 20: 175–180.
- List AF, Spier CM, Cline A, Doll DC, Garewal H, Morgan R et al. 1991. Expression of the multidrug resistance gene product (P-glycoprotein) in myelodysplasia is associated with a stem cell phenotype. Br J Haematol 78: 28–34.
- te Boekhorst PA, de Leeuw K, Schoester M, Wittebol S, Nooter K, Hagemeijer A et al. 1993. Predominance of functional multidrug resistance (MDR-1) phenotype in CD34+ acute myeloid leukemia cells. Blood 82: 3157–3162.
- Paietta E, Andersen J, Racevskis J, Gallagher R, Bennett J, Yunis J et al. 1994. Significantly lower P-glycoprotein expression in acute promyelocytic leukemia than in other types of acute myeloid leukemia: Immunological, molecular and functional analyses. Leukemia 8: 968–973.
- Legrand O, Simonin G, Perrot JY, Zittoun R, and Marie JP. 1999. Both P-gp and MRP1 activities using calcein-AM contribute to drug resistance in AML. Adv Exp Med Biol 457: 161–175.
- Steinbach D and Legrand O. 2007. ABC transporters and drug resistance in leukemia: Was P-gp nothing but the first head of the Hydra? Leukemia 21: 1172–1176.
- Ponte-Sucre A. 2007. Availability and applications of ATP-binding cassette (ABC) transporter blockers. Appl Microbiol Biotechnol 76: 279–286.
- Mahadevan D and List AF. 2004. Targeting the multidrug resistance-1 transporter in AML: Molecular regulation and therapeutic strategies. Blood 104: 1940–1951.
- Tsuruo T, Iida H, Tsukagoshi S, and Sakurai Y. 1981. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41: 1967–1972.
- Krishna R and Mayer LD. 2001. Modulation of P-glycoprotein (P-gp) mediated multidrug resistance (MDR) using chemosensitizers: Recent advances in the design of selective MDR modulators. Curr Med Chem Anti-Canc Agents 1: 163–174.
- Solary E, Caillot D, Chauffert B, Casasnovas RO, Dumas M, Maynadie M et al. 1992. Feasibility of using quinine, a potential multidrug resistance-reversing agent, in combination with mitoxantrone and cytarabine for the treatment of acute leukemia. J Clin Oncol 10: 1730–1736.
- Marie JP, Bastie JN, Coloma F, Faussat Suberville AM, Delmer A, Rio B et al. 1993. Cyclosporin A as a modifier agent in the salvage treatment of acute leukemia (AL). Leukemia 7: 821–824.
- Xu WL, Shen HL, Ao ZF, Chen BA, Xia W, Gao F et al. 2006. Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia. Leuk Res 30: 407–413.
- Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY et al. 1996. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: A randomized multicenter study. Blood 88: 1198–1205.
- Wattel E, Solary E, Hecquet B, Caillot D, Ifrah N, Brion A et al. 1999. Quinine improves results of intensive chemotherapy in myelodysplastic syndromes expressing P-glycoprotein: Updated results of a randomized study. Groupe Francais des Myleodysplasies (GFM) and Groupe GOELAMS. Adv Exp Med Biol 457: 35–46.
- Solary E, Drenou B, Campos L, de Crémoux P, Mugneret F, Moreau P et al. 2003. Quinine as a multidrug resistance inhibitor: A phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia. Blood 102: 1202–1210.
- Liu Yin JA, Wheatley K, Rees JK, and Burnett AK. 2001. Comparison of “sequential” versus “standard” chemotherapy as re-induction treatment, with or without cyclosporine, in refractory/relapsed acute myeloid leukaemia (AML): Results of the UK Medical Research Council AML-R trial. Br J Haematol 113: 713–726.
- List AF, Kopecky KJ, Willman CL, Head DR, Persons DL, Slovak ML et al. 2001. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: A Southwest Oncology Group study. Blood 98: 3212–3220.
- Sonneveld P, Burnett A, Vossebeld P, Ben-Am M, Rosenkranz G, Pfister C et al. 2000. Dose-finding study of valspodar (PSC 833) with daunorubicin and cytarabine to reverse multidrug resistance in elderly patients with previously untreated acute myeloid leukemia. Hematol J 1: 411–421.
- Advani R, Saba HI, Tallman MS, Rowe JM, Wiernik PH, Ramek J et al. 1999. Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (valspodar). Blood 93: 787–795.
- Baer MR, George SL, Dodge RK, O'Loughlin KL, Minderman H, Caligiuri MA et al. 2002. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood 100: 1224–1232.
- Sonneveld P and List AF. 2001. Chemotherapy resistance in acute myeloid leukaemia. Best Pract Res Clin Haematol 14: 211–233.
- Goldman B. 2003. Multidrug resistance: Can new drugs help chemotherapy against cancer? J Natl Cancer Inst 95: 255–257.
- Thomas H and Coley HM. 2003. Overcoming multidrug resistance in cancer: An update on the clinical strategy of inhibiting P-glycoprotein. Cancer Control 10: 159–165.
- Morschhauser F, Zinzani PL, Burgess M, Sloots L, Bouafia F, and Dumontet C. 2007. Phase I/II trial of a P-glycoprotein inhibitor, Zosuquidar.3HCl trihydrochloride (LY335979), given orally in combination with the CHOP regimen in patients with non-Hodgkin's lymphoma. Leuk Lymphoma 48: 708–715.
- Hoover RR, Mahon FX, Melo JV, and Daley GQ. 2002. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood 100: 1068–1071.
- Kabanov AV, Batrakova EV, and Alahov VY. 2002. Pluonic block copolymers for overcoming drug resistance in cancer. Adv Drug Delivery Rev 54: 759–779.
- Pawlak-Roblin C, Tosi PF, Perrin L, Devy J, Venteo L, Albert P et al. 2004. Inhibition of multidrug resistance by immunization with synthetic P-glycoprotein-derived peptides. Eur J Cancer 40: 606–613.
- Cole SP, Sparks KE, Fraser K, Loe DW, Grant CE, Wilson GM et al. 1994. Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res 54: 5902–5910.
- Leith CP, Kopecky KJ, Chen IM, Eijdems L, Slovak ML, McConnell TS et al. 1999. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: A Southwest Oncology Group Study. Blood 94: 1086–1099.
- Legrand O, Simonin G, Beauchamp-Nicoud A, Zittoun R, and Marie JP. 1999. Simultaneous activity of MRP1 and PGP is correlated with in vitro resistance to daunorubicin and with in vivo resistance in adult acute myeloid leukemia. Blood 94: 1046–1056.
- Filipits M, Suchomel RW, Zöchbauer S, Brunner R, Lechner K, and Pirker R. 1997. Multidrug resistance-associated protein in acute myeloid leukemia: No impact on treatment outcome. Clin Cancer Res 3: 1419–1425.
- van den Heuvel-Eibrink MM, van der Holt B, Burnett AK, Knauf WU, Fey MF, Verhoef GE et al. 2007. CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age. Ann Hematol 86: 329–337.
- Walter RB, Raden BW, Hong TC, Flowers DA, Bernstein ID, and Linenberger ML. 2003. Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells. Blood 102: 1466–1473.
- Burger H, Nooter K, Zaman GJ, Sonneveld P, van Wingerden KE, Oostrum RG et al. 1994. Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias. Leukemia 8: 990–997.
- Kim HS, Min YD, and Choi CH. 2001. Double-edged sword of chemosensitizer: Increase of multidrug resistance protein (MRP) in leukemic cells by an MRP inhibitor probenecid. Biochem Biophys Res Commun 283: 64–71.
- O'Connor R, O'Leary M, Ballot J, Collins CD, Kinsella P, Mager DE et al. 2007. A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer. Cancer Chemother Pharmacol 59: 79–87.
- Germann UA, Ford PJ, Shlyakhter D, Mason VS, and Harding MW. 1997. Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP. Anticancer Drugs 8: 141–155.
- Sun M, Xu X, Lu Q, Pan Q, and Hu X. 2007. Schisandrin B: A dual inhibitor of P-glycoprotein and multidrug resistance-associated protein 1. Cancer Lett 246: 300– 307.
- Raaijmakers MKGP. 2007. ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutic targets in acute and chronic myeloid leukaemia. Leukemia 21: 2094–2102.
- Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J et al. 1994. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367: 645–648.
- Bonnet D and Dick JE. 1997. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3: 730–737.
- Holyoake T, Jiang X, Eaves C, and Eaves A. 1999. Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood 94: 2056–2064.
- Cobaleda C, Gutiérrez-Cianca N, Pérez-Losada J, Flores T, García-Sanz R, González M et al. 2000. A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia. Blood 95: 1007–1013.
- Nilsson L, Astrand-Grundström I, Anderson K, Arvidsson I, Hokland P, Bryder D et al. 2002. Involvement and functional impairment of the CD34(+)CD38(−) Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood 100: 259–267.
- Gal H, Amariglio N, Trakhtenbrot L, Jacob-Hirsh J, Margalit O, Avigdor A et al. 2006. Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells. Leukemia 20: 2147–2154.
- Feuring-Buske M and Hogge DE. 2001. Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34(+)CD38(−) progenitor cells from patients with acute myeloid leukemia. Blood 97: 3882–3889.
- Raaijmakers MH, de Grouw EP, Heuver LH, van der Reijden BA, Jansen JH, Scheper RJ et al. 2005. Breast cancer resistance protein in drug resistance of primitive CD34 + 38− cells in acute myeloid leukemia. Clin Cancer Res 11: 2436–2444.
- van der Kolk DM, Vellenga E, Scheffer GL, Müller M, Bates SE, Scheper RJ et al. 2002. Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia. Blood 99: 3763–3770.
- Allen JD, van Loevezijn A, Lakhai JM, van der Valk M, van Tellingen O, Reid G et al. 2002. Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther 1: 417–425.
- Mannervik B and Danielson UH. 1988. Glutathione transferases—and catalytic activity. CRC Crit Rev Biochem 23: 283–337.
- Lo HW and Ali-Osman F. 2007. Genetic polymorphism and function of glutathi-one S-transferases in tumor drug resistance. Curr Opin Pharmacol 7: 367–374.
- Bennaceur-Griscelli A, Bosq J, Koscielny S, Lefrère F, Turhan A, Brousse N et al. 2004. High level of glutathione-S-transferase pi expression in mantle cell lymphomas. Clin Cancer Res 10: 3029–3034.
- Ribrag V, Koscielny S, Carpiuc I, Cebotaru C, Vande Walle H, Talbot M et al. 2003. Prognostic value of GST-pi expression in diffuse large B-cell lymphomas. Leukemia 17: 972–977.
- Tew KD, O'Brien M, Laing NM, and Shen H. 1998. Coordinate changes in expression of protective genes in drug-resistant cells. Chem Biol Interact 111–112: 199–211.
- Tew KD. 2007. Redox in redux: Emergent roles for glutathione S-transferase P (GSTP) in regulation of cell signaling and S-glutathionylation. Biochem Pharmacol 73: 1257–1269.
- Davis Jr. W, Ronai Z, and Tew KD. 2001. Cellular thiols and reactive oxygen species in drug-induced apoptosis. J Pharmacol Exp Ther 296: 1–6.
- Ono K and Han J. 2000. The p38 signal transduction pathway: Activation and function. Cell Signal 12: 1–13.
- Kodym R, Calkins P, and Story M. 1999. The cloning and characterization of a new stress response protein. A mammalian member of a family of theta class glutathione s-transferase-like proteins. J Biol Chem 274: 5131–5137.
- Voehringer DW, Hirschberg DL, Xiao J, Lu Q, Roederer M, Lock CB et al. 2000. Gene microarray identification of redox and mitochondrial elements that control resistance or sensitivity to apoptosis. Proc Natl Acad Sci U S A 97: 2680–2685.
- Cumming RC, Lightfoot J, Beard K, Youssoufian H, O'Brien PJ, and Buchwald M. 2001. Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1. Nat Med 7: 814–820.
- Cho SG, Lee YH, Park HS, Ryoo K, Kang KW, Park J et al. 2001. Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. J Biol Chem 276: 12749–12755.
- O'Dwyer PJ, LaCreta F, Nash S, Tinsley PW, Schilder R, Clapper ML et al. 1991. Phase I study of thiotepa in combination with the glutathione transferase inhibitor ethacrynic acid. Cancer Res 51: 6059–6065.
- Petrini M, Conte A, Caracciolo F, Sabbatini A, Grassi B, and Ronca G. 1993. Reversing of chlorambucil resistance by ethacrynic acid in a B-CLL patient. Br J Haematol 85: 409–410.
- Mulder GJ and Ouwerkerk-Mahadevan S. 1997. Modulation of glutathione conjugation in vivo: How to decrease glutathione conjugation in vivo or in intact cellular systems in vitro. Chem Biol Interact 105: 17–34.
- Oakley AJ, Lo Bello M, Mazzetti AP, Federici G, and Parker MW. 1997. The glutathione conjugate of ethacrynic acid can bind to human pi class glutathione transferase P1-1 in two different modes. FEBS Lett 419: 32–36.
- Lyttle MH, Hocker MD, Hui HC, Caldwell CG, Aaron DT, Engqvist-Goldstein A et al. 1994. Isozyme-specific glutathione-S-transferase inhibitors: Design and synthesis. J Med Chem 37: 189–194.
- Lyttle MH, Aaron DT, Hocker MD, and Hughes BR. 1992. Construction of affinity sorbents utilizing glutathione analogs. Pept Res 5: 336–342.
- O'Brien ML, Vulevic B, Freer S, Boyd J, Shen H, and Tew KD. 1999. Glutathione peptidomimetic drug modulator of multidrug resistance-associated protein. J Pharmacol Exp Ther 291: 1348–1355.
- Ruscoe JE, Rosario LA, Wang T, Gaté L, Arifoglu P, Wolf CR et al. 2001. Pharmacologic or genetic manipulation of glutathione S-transferase P1-1 (GSTpi) influences cell proliferation pathways. J Pharmacol Exp Ther 298: 339–345.
- Naing A, Sokol L, and List AF. 2006. Developmental therapeutics for myelodysplastic syndromes. J Natl Compr Canc Netw 4: 78–82.
- Turella P, Filomeni G, Dupuis ML, Ciriolo MR, Molinari A, De Maria F et al. 2006. A strong glutathione S-transferase inhibitor overcomes the P-glycoprotein-mediated resistance in tumor cells. 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) triggers a caspase-dependent apoptosis in MDR1-expressing leukemia cells. J Biol Chem 281: 23725–23732.
- Gunnarsdottir S and Elfarra AA. 2004. Cytotoxicity of the novel glutathione-activated thiopurine prodrugs cis-AVTP [cis-6-(2-acetylvinylthio)purine] and trans-AVTG [trans-6-(2-acetylvinylthio)guanine] results from the National Cancer Institute's anticancer drug screen. Drug Metab Dispos 32: 321–327.
- Tew KD. 2005. TLK-286: A novel glutathione S-transferase-activated prodrug. Expert Opin Investig Drugs 14: 1047–1054.
- Kavanagh JJ, Gershenson DM, Choi H, Lewis L, Patel K, Brown GL et al. 2005. Multi-institutional phase 2 study of TLK286 (TELCYTA, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer. Int J Gynecol Cancer 15: 593–600.
- Raez LE and Lilenbaum R. 2006. New developments in chemotherapy for advanced non-small cell lung cancer. Curr Opin Oncol 18: 156–161.
- Seow HA, Penketh PG, Shyam K, Rockwell S, and Sartorelli AC. 2005. 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl] hydra-zine: An anticancer agent targeting hypoxic cells. Proc Natl Acad Sci U S A 102: 9282–9287.
- Liu J, Li C, Qu W, Leslie E, Bonifant CL, Buzard GS et al. 2004. Nitric oxide prodrugs and metallochemotherapeutics: JS-K and CB-3-100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation. Mol Cancer Ther 3: 709–714.
- Findlay VJ, Townsend DM, Saavedra JE, Buzard GS, Citro ML, Keefer LK et al. 2004. Tumor cell responses to a novel glutathione S-transferase-activated nitric oxide-releasing prodrug. Mol Pharmacol 65: 1070–1079.
- Stanulla M, Schrappe M, Brechlin AM, Zimmermann M, and Welte K. 2000. Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: A case-control study. Blood 95: 1222–1228.
- Aguirre-Ghiso JA. 2007. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7: 834–846.
- Talpaz M, Estrov Z, Kantarjian H, Ku S, Foteh A, and Kurzrock R. 1994. Persistence of dormant leukemic progenitors during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies. J Clin Invest 94: 1383–1389.
- Saudemont A and Quesnel B. 2004. In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis. Blood 104: 2124–2133.
- Saudemont A, Hamrouni A, Marchetti P, Liu J, Jouy N, Hetuin D et al. 2007. Dormant tumor cells develop cross-resistance to apoptosis induced by CTLs or imatinib mesylate via methylation of suppressor of cytokine signaling 1. Cancer Res 67: 4491–4498.
- Indraccolo S, Stievano L, Minuzzo S, Tosello V, Esposito G, Piovan E et al. 2006. Interruption of tumor dormancy by a transient angiogenic burst within the tumor microenvironment. Proc Natl Acad Sci U S A 103: 4216–4221.
- Naumov GN, Akslen LA, and Folkman J. 2006. Role of angiogenesis in human tumor dormancy: Animal models of the angiogenic switch. Cell Cycle 5: 1779–1787.
- Marches R, Hsueh R, and Uhr JW. 1999. Cancer dormancy and cell signaling: Induction of p21 (waf1) initiated by membrane IgM engagement increases survival of B lymphoma cells. Proc Natl Acad Sci U S A 96: 8711–8715.
- Aguirre Ghiso JA. 2002. Inhibition of FAK signaling activated by urokinase receptor induces dormancy in human carcinoma cells in vivo. Oncogene 21: 2513–2524.
- Ranganathan AC, Zhang L, Adam AP, and Aguirre-Ghiso JA. 2006. Functional coupling of p38-induced up-regulation of BiP and activation of RNA-dependent protein kinase-like endoplasmic reticulum kinase to drug resistance of dormant carcinoma cells. Cancer Res 66: 1702–1711.
- Jordheim LP and Dumontet C. 2007. Review of recent studies on resistance to cytotoxic deoxynucleoside analogues. Biochim Biophys Acta 1776: 138–159.
- Hunsucker SA, Spychala J, and Mitchell BS. 2001. Human cytosolic 5′-nucleotidase I: Characterization and role in nucleoside analog resistance. J Biol Chem 276: 10498–10504.
- Kodama K, Morozumi M, Saitoh K, Kuninaka A, Yoshino H, and Saneyoshi M. 1989. Antitumor activity and pharmacology of 1-beta-D-arabinofuranosylcytosine-5′-stearylphosphate: An orally active derivative of 1-beta-D-arabinofuranosylcytosine. Jpn J Cancer Res 80: 679–685.
- Cheon EP, Hong JH, and Han HK. 2006. Enhanced cellular uptake of Ara-C via a peptidomimetic prodrug, L-valyl-ara-C in Caco-2 cells. J Pharm Pharmacol 58: 927–932.
- Haberkorn U, Oberdorfer F, Gebert J, Morr I, Haack K et al. 1996. Monitoring gene therapy with cytosine deaminase: In vitro studies using tritiated-5-fluorocytosine. J Nucl Med 37: 87–94.
- SenGupta DJ and Unadkat JD. 2004. Glycine 154 of the equilibrative nucleoside transporter, hENT1, is important for nucleoside transport and for conferring sensitivity to the inhibitors nitrobenzylthioinosine, dipyridamole, and dilazep. Biochem Pharmacol 67: 453–438.
- Hubeek I, Stam RW, Peters GJ, Broekhuizen R, Meijerink JP, van Wering ER et al. 2005. The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia. Br J Cancer 93: 1388–1394.
- Takagaki K, Katsuma S, Kaminishi Y, Horio T, Nakagawa S, Tanaka T et al. 2004. Gene-expression profiling reveals down-regulation of equilibrative nucleoside transporter 1 (ENT1) in Ara-C-resistant CCRF-CEM-derived cells. J Biochem 136: 733–740.
- Galmarini CM, Mackey JR, and Dumontet C. 2002. Nucleoside analogues and nucleobases in cancer treatment. Lancet Oncol 3: 415–424.
- Gandhi V, Plunkett W, Weller S, Du M, Ayres M, Rodriguez CO Jr. et al. 2001. Evaluation of the combination of nelarabine and fludarabine in leukemias: Clinical response, pharmacokinetics, and pharmacodynamics in leukemia cells. J Clin Oncol 19: 2142–2152.
- Spasokoukotskaja T, Sasvári-Székely M, Keszler G, Albertioni F, Eriksson S, and Staub M. 1999. Treatment of normal and malignant cells with nucleoside analogues and etoposide enhances deoxycytidine kinase activity. Eur J Cancer 35: 1862–1867.
- Galmarini CM, Clarke ML, Santos CL, Jordheim L, Perigaud C, Gosselin G et al. 2003. Sensitization of ara-C-resistant lymphoma cells by a pronucleotide analogue. Int J Cancer 107: 149–154.
- Ravandi F, Kantarjian H, Giles F, and Cortes J. 2004. New agents in acute myeloid leukemia and other myeloid disorders. Cancer 100: 441–454.
- Kantarjian HM, Jeha S, Gandhi V, Wess M, and Faderl S. 2007. Clofarabine: Past, present, and future. Leuk Lymphoma 48: 1922–1930.
- Swords R and Giles F. 2007. Troxacitabine in acute leukemia. Hematology 12: 219–227.
- Burtness B, Belker M, Stoltz M, Peccerillo KM, Lamb LA, Chmael SE et al. 2000. A phase I study of the antimetabolite (E)-2′-fluoromethylene-2′-deoxycytidine (MDL 101,731) administered as a twice-weekly infusion. Cancer J 6: 309–315.
- Juliusson G and Liliemark J. 2006. Purine analogues: Rationale for development, mechanisms of action, and pharmacokinetics in hairy cell leukemia. Hematol Oncol Clin North Am 20: 1087–1097.
- Månsson E, Flordal E, Liliemark J, Spasokoukotskaja T, Elford H, Lagercrantz S et al. 2003. Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance. Biochem Pharmacol 65: 237–247.
- Wang J, Lohman GJ, and Stubbe J. 2007. Enhanced subunit interactions with gemcitabine-5′-diphosphate inhibit ribonucleotide reductases. Proc Natl Acad Sci U S A 104: 14324–14329.
- Genini D, Budihardjo I, Plunkett W, Wang X, Carrera CJ, Cottam HB et al. 2000. Nucleotide requirements for the in vitro activation of the apoptosis protein-activating factor-1-mediated caspase pathway. J Biol Chem 275: 29–34.
- Genini D, Adachi S, Chao Q, Rose DW, Carrera CJ, Cottam HB et al. 2000. Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria. Blood 96: 3537–3543.
- Klöpfer A, Hasenjäger A, Belka C, Schulze-Osthoff K, Dörken B, and Daniel PT. 2004. Adenine deoxynucleotides fludarabine and cladribine induce apoptosis in a CD95/Fas receptor, FADD and caspase-8-independent manner by activation of the mitochondrial cell death pathway. Oncogene 23: 9408–9418.
- Lu C and Hassan HT. 2006. Human stem cell factor-antibody [anti-SCF] enhances chemotherapy cytotoxicity in human CD34+ resistant myeloid leukaemia cells. Leuk Res 30: 296–302.
- Robak T. 2007. Recent progress in the management of chronic lymphocytic leukemia. Cancer Treat Rev 33: 710–728.
- Druker BJ and Lydon NB. 2000. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 105: 3–7.
- Apperley JF. 2007. Part I: Mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 8: 1018–1029.
- van Erp NP, Gelderblom H, Karlsson MO, Li J, Zhao M, Ouwerkerk J et al. 2007. Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib. Clin Cancer Res 13: 7394–7400.
- Gambacorti-Passerini C, Barni R, le Coutre P, Zucchetti M, Cabrita G, Cleris L et al. 2000. Role of alpha1 acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor STI571. J Natl Cancer Inst 92: 1641–1650.
- Jørgensen HG, Elliott MA, Allan EK, Carr CE, Holyoake TL, and Smith KD. 2002. Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI571. Blood 99: 713–715.
- White DL, Saunders VA, Dang P, Engler J, Venables A, Zrim S et al. 2007. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: Higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood 110: 4064–4072.
- Jordanides NE, Jorgensen HG, Holyoake TL, and Mountford JC. 2006. Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood 108: 1370–1373.
- Gardner ER, Burger H, van Schaik RH, van Oosterom AT, de Bruijn EA, Guetens G et al. 2006. Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther 80: 192–201.
- Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN et al. 2001. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293: 876–880.
- Branford S, Rudzki Z, Walsh S, Grigg A, Arthur C, Taylor K et al. 2002. High 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) resistance. Blood 99: 3472–3475.
- Hochhaus A. 2007. Dasatinib for the treatment of Philadelphia chromosome-positive chronic myelogenous leukaemia after imatinib failure. Expert Opin Pharmacother 8: 3257–3264.
- Quintás-Cardama A, Kantarjian H, and Cortes J. 2007. Flying under the radar: The new wave of BCR-ABL inhibitors. Nat Rev Drug Discov 6: 834–848.
- Apperley JF. 2007. Part II: Management of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 8: 1116–1128.
- Barnes DJ and Melo JV. 2006. Primitive, quiescent and difficult to kill: The role of non-proliferating stem cells in chronic myeloid leukemia. Cell Cycle 5: 2862–2866.
- Hoover RR, Mahon FX, Melo JV, and Daley GQ. 2002. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood 100: 1068–1071.
- Cortes J and Kantarjian H. 2005. New targeted approaches in chronic myeloid leukemia. J Clin Oncol 23: 6316–6324.
- Boschelli DH, Wu B, Ye F, Wang Y, Golas JM, Lucas J et al. 2006. Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl) amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem 49: 7868–7876.
- Yokota A, Kimura S, Masuda S, Ashihara E, Kuroda J, Sato K et al. 2007. INNO-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 activity. Blood 109: 306–314.
- Gumireddy K, Baker SJ, Cosenza SC, John P, Kang AD, and Robell KA. 2005. A non-ATP-competitive inhibitor of BCR-ABL overrides imatinib resistance. Proc Natl Acad Sci U S A 102: 1992–1997.
- Adrián FJ, Ding Q, Sim T, Velentza A, Sloan C, Liu Y et al. 2006. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol 2: 95–102.
- Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, and Freedman SJ. 2007. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood 15 (109): 500–502.
- Legros L, Hayette S, Nicolini FE, Raynaud S, Chabane K, Magaud JP et al. 2007. BCR-ABL(T315I) transcript disappearance in an imatinib-resistant CML patient treated with homoharringtonine: A new therapeutic challenge? Leukemia 21: 2204–2206.
- Carter TA, Wodicka LM, Shah NP, Velasco AM, Fabian MA, Treiber DK et al. 2005. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci U S A 102: 11011–11016.
- Reed JC and Pellecchia M. 2005. Apoptosis-based therapies for hematologic malignancies. Blood 106: 408–418.
- Schimmer AD. 2007. Novel therapies targeting the apoptosis pathway for the treatment of acute myeloid leukemia. Curr Treat Options Oncol 8: 277–286.
- Wu H, Tschopp J, and Lin SC. 2007. Smac mimetics and TNFalpha: A dangerous liaison? Cell 131: 655–658.
- Tolcher AW, Mita M, Meropol NJ, von Mehren M, Patnaik A, Padavic K et al. 2007. Phase I pharmacokinetic and biologic correlative study of mapatumumab, a fully human monoclonal antibody with agonist activity to tumor necrosis factor-related apoptosis-inducing ligand receptor-1. J Clin Oncol 25: 1390–1395.
- Nguyen M, Marcellus RC, Roulston A, Watson M, Serfass L, Murthy Madiraju SR et al. 2007. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci U S A 104: 19512–19517.
- Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S et al. 2006. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 10: 375–388.
- Kuroda J, Kimura S, Andreeff M, Ashihara E, Kamitsuji Y, Yokota A et al. 2008. ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms. Br J Haematol 140: 181–190.
- Del Gaizo Moore V, Schlis KD, Sallan SE, Armstrong SA, and Letai A. 2008. BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood 111: 2300–2309.
- Matsunaga T, Fukai F, Miura S, Nakane Y, Owaki T, Kodama H et al. 2008. Combination therapy of an anticancer drug with the FNIII14 peptide of fibronectin effectively overcomes cell adhesion-mediated drug resistance of acute myelogenous leukemia. Leukemia 22: 353–360.
- Sujobert P, Bardet V, Cornillet-Lefebvre P, Hayflick JS, Prie N, Verdier F et al. 2005. Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukaemia. Blood 106: 1063–1066.
- Martelli AM, Nyakern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C et al. 2006. Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 20: 911–928.
- Tamburini J, Chapuis N, Bardet V, Park S, Sujobert P, Willems L et al. 2008. 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. Blood 111: 379–382.
- Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL et al. 2007. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13: 54–61.
- Tesniere A, Panaretakis T, Kepp O, Apetoh L, Ghiringhelli F, Zitvogel L et al. 2008. Molecular characteristics of immunogenic cancer cell death. Cell Death Differ 15: 3–12.
- Vink J, Cloos J, and Kaspers GJ. 2006. Proteasome inhibition as novel treatment strategy in leukaemia. Br J Haematol 134: 253–262.
- Mitsiades N, Mitsiades CS, Richardson PG, Poulaki V, Tai YT, Chauhan D et al. 2003. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: Therapeutic applications. Blood 101: 2377–2380.
- Landis-Piwowar KR, Milacic V, Chen D, Yang H, Zhao Y, Chan TH et al. 2006. The proteasome as a potential target for novel anticancer drugs and chemosensitizers. Drug Resist Updat 9: 263–273.
- Sillaber C, Mayerhofer M, Böhm A, Vales A, Gruze A, Aichberger KJ et al. 2008. Evaluation of antileukaemic effects of rapamycin in patients with imatinib-resistant chronic myeloid leukaemia. Eur J Clin Invest 38: 43–52.
- Maggio SC, Rosato RR, Kramer LB, Dai Y, Rahmani M, Paik DS et al. 2004. The histone deacetylase inhibitor MS-275 interacts synergistically with fludarabine to induce apoptosis in human leukemia cells. Cancer Res 64: 2590–2600.
- Kihslinger JE and Godley LA. 2007. The use of hypomethylating agents in the treatment of hematologic malignancies. Leuk Lymphoma 48: 1676–1695.
- Stam RW, den Boer ML, Schneider P, Nollau P, Horstmann M, Beverloo HB et al. 2005. Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia. Blood 106: 2484–2490.
- McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F et al. 2007. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 1773: 1263–1284.
