Background Resistance to imatinib mesylate can occur in chronicmyelogenous leukemia (CML). Preclinical in vitro studies haveshown that nilotinib (AMN107), a new BCR-ABL tyrosine kinaseinhibitor, is more potent than imatinib against CML cells bya factor of 20 to 50.
Methods In a phase 1 dose-escalation study, we assigned 119patients with imatinib-resistant CML or acute lymphoblasticleukemia (ALL) to receive nilotinib orally at doses of 50 mg,100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once dailyand at 400 mg and 600 mg twice daily.
Results Common adverse events were myelosuppression, transientindirect hyperbilirubinemia, and rashes. Of 33 patients withthe blastic phase of disease, 13 had a hematologic responseand 9 had a cytogenetic response; of 46 patients with the acceleratedphase, 33 had a hematologic response and 22 had a cytogeneticresponse; 11 of 12 patients with the chronic phase had a completehematologic remission.
Conclusions Nilotinib has a relatively favorable safety profileand is active in imatinib-resistant CML. (ClinicalTrials.govnumber, NCT00109707
[ClinicalTrials.gov]
.)
Source Information
From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (H.K., F.G., S.O., J.C.); J.W. Goethe Universität, Frankfurt, Germany (L.W., B.W., D.H., O.G.O.); Moffitt Cancer Center, Tampa, Fla. (K.B.); Novartis Pharmaceuticals, East Hanover, N.J. (C.T., P.M., P.R., W.M., K.B., M.D., L.A.); Quest Diagnostics, San Juan Capistrano, Calif. (M.A.); Fakultät fur Klinische Medizin Mannheim, Universität Heidelberg, Mannheim, Germany (A.H.); and the Department of Medical Oncology, Dana–Farber Cancer Institute, Boston (J.D.G.). Drs. Kantarjian and Giles contributed equally to this article.
Address reprint requests to Dr. Kantarjian at the Department of Leukemia, Unit 428, University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Houston, TX 77230-1402, or at hkantarj{at}mdanderson.org.
Yeh, E. T.H., Bickford, C. L.
(2009). Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management.. J Am Coll Cardiol
53: 2231-2247
[Abstract][Full Text]
Baccarani, M., Dreyling, M., On behalf of the ESMO Guidelines Working Group,
(2009). Chronic myelogenous leukemia: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol
20: iv105-iv107
[Full Text]
Seeliger, M. A., Ranjitkar, P., Kasap, C., Shan, Y., Shaw, D. E., Shah, N. P., Kuriyan, J., Maly, D. J.
(2009). Equally Potent Inhibition of c-Src and Abl by Compounds that Recognize Inactive Kinase Conformations. Cancer Res.
69: 2384-2392
[Abstract][Full Text]
Carlomagno, F., Guida, T., Anaganti, S., Provitera, L., Kjaer, S., McDonald, N. Q, Ryan, A. J, Santoro, M.
(2009). Identification of tyrosine 806 as a molecular determinant of RET kinase sensitivity to ZD6474. Endocr Relat Cancer
16: 233-241
[Abstract][Full Text]
Quintas-Cardama, A., Cortes, J.
(2009). Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood
113: 1619-1630
[Abstract][Full Text]
Yong, A. S. M., Keyvanfar, K., Hensel, N., Eniafe, R., Savani, B. N., Berg, M., Lundqvist, A., Adams, S., Sloand, E. M., Goldman, J. M., Childs, R., Barrett, A. J.
(2009). Primitive quiescent CD34+ cells in chronic myeloid leukemia are targeted by in vitro expanded natural killer cells, which are functionally enhanced by bortezomib. Blood
113: 875-882
[Abstract][Full Text]
Jones, D., Kamel-Reid, S., Bahler, D., Dong, H., Elenitoba-Johnson, K., Press, R., Quigley, N., Rothberg, P., Sabath, D., Viswanatha, D., Weck, K., Zehnder, J.
(2009). Laboratory Practice Guidelines for Detecting and Reporting BCR-ABL Drug Resistance Mutations in Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia: A Report of the Association for Molecular Pathology. J. Mol. Diagn.
11: 4-11
[Abstract][Full Text]
Cortes, J.
(2009). When Imatinib Fails, What Else Is There?. Am Soc Clin Oncol Ed Book
2009: 402-406
[Abstract][Full Text]
O'Hare, T., Deininger, M. W.
(2008). Toward a Cure For Chronic Myeloid Leukemia. Clin. Cancer Res.
14: 7971-7974
[Full Text]
Druker, B. J.
(2008). Translation of the Philadelphia chromosome into therapy for CML. Blood
112: 4808-4817
[Abstract][Full Text]
Jabbour, E., Kantarjian, H. M., Jones, D., Reddy, N., O'Brien, S., Garcia-Manero, G., Burger, J., Cortes, J.
(2008). Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors. Blood
112: 4839-4842
[Abstract][Full Text]
Hehlmann, R., Saussele, S.
(2008). Treatment of chronic myeloid leukemia in blast crisis. haematol
93: 1765-1769
[Full Text]
Palandri, F., Castagnetti, F., Testoni, N., Luatti, S., Marzocchi, G., Bassi, S., Breccia, M., Alimena, G., Pungolino, E., Rege-Cambrin, G., Varaldo, R., Miglino, M., Specchia, G., Zuffa, E., Ferrara, F., Bocchia, M., Saglio, G., Pane, F., Alberti, D., Martinelli, G., Baccarani, M., Rosti, G., on behalf of the GIMEMA Working Party on Chronic M,
(2008). Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up. haematol
93: 1792-1796
[Abstract][Full Text]
Marin, D., Milojkovic, D., Olavarria, E., Khorashad, J. S., de Lavallade, H., Reid, A. G., Foroni, L., Rezvani, K., Bua, M., Dazzi, F., Pavlu, J., Klammer, M., Kaeda, J. S., Goldman, J. M., Apperley, J. F.
(2008). European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood
112: 4437-4444
[Abstract][Full Text]
Williams, R.T., Sherr, C.J.
(2008). The INK4-ARF (CDKN2A/B) Locus in Hematopoiesis and BCR-ABL-induced Leukemias. Cold Spring Harb Symp Quant Biol
0: sqb.2008.73.039v2-sqb.2008.73.039
[Abstract]
Acquaviva, J., Chen, X., Ren, R.
(2008). IRF-4 functions as a tumor suppressor in early B-cell development. Blood
112: 3798-3806
[Abstract][Full Text]
Bewry, N. N., Nair, R. R., Emmons, M. F., Boulware, D., Pinilla-Ibarz, J., Hazlehurst, L. A.
(2008). Stat3 contributes to resistance toward BCR-ABL inhibitors in a bone marrow microenvironment model of drug resistance. Molecular Cancer Therapeutics
7: 3169-3175
[Abstract][Full Text]
Distler, J. H. W., Distler, O.
(2008). Intracellular tyrosine kinases as novel targets for anti-fibrotic therapy in systemic sclerosis. Rheumatology (Oxford)
47: v10-v11
[Abstract][Full Text]
Levine, R. L., Gilliland, D. G.
(2008). Myeloproliferative disorders. Blood
112: 2190-2198
[Abstract][Full Text]
Veldurthy, A., Patz, M., Hagist, S., Pallasch, C. P., Wendtner, C.-M., Hallek, M., Krause, G.
(2008). The kinase inhibitor dasatinib induces apoptosis in chronic lymphocytic leukemia cells in vitro with preference for a subgroup of patients with unmutated IgVH genes. Blood
112: 1443-1452
[Abstract][Full Text]
Frohling, S., Dohner, H.
(2008). Chromosomal Abnormalities in Cancer. NEJM
359: 722-734
[Full Text]
Quintas-Cardama, A., Cortes, J.
(2008). Therapeutic Options Against BCR-ABL1 T315I-Positive Chronic Myelogenous Leukemia. Clin. Cancer Res.
14: 4392-4399
[Abstract][Full Text]
Akhmetshina, A., Dees, C., Pileckyte, M., Maurer, B., Axmann, R., Jungel, A., Zwerina, J., Gay, S., Schett, G., Distler, O., Distler, J. H. W.
(2008). Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib for the treatment of dermal fibrosis. FASEB J.
22: 2214-2222
[Abstract][Full Text]
Deininger, M. W.
(2008). Nilotinib. Clin. Cancer Res.
14: 4027-4031
[Full Text]
Jabbour, E., Kantarjian, H., Jones, D., Breeden, M., Garcia-Manero, G., O'Brien, S., Ravandi, F., Borthakur, G., Cortes, J.
(2008). Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy. Blood
112: 53-55
[Abstract][Full Text]
Mullighan, C. G., Williams, R. T., Downing, J. R., Sherr, C. J.
(2008). Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL. Genes Dev.
22: 1411-1415
[Abstract][Full Text]
Steeghs, N., Gelderblom, H., Roodt, J. o. t, Christensen, O., Rajagopalan, P., Hovens, M., Putter, H., Rabelink, T. J., de Koning, E.
(2008). Hypertension and Rarefaction during Treatment with Telatinib, a Small Molecule Angiogenesis Inhibitor. Clin. Cancer Res.
14: 3470-3476
[Abstract][Full Text]
Samudio, I., Kurinna, S., Ruvolo, P., Korchin, B., Kantarjian, H., Beran, M., Dunner, K. Jr., Kondo, S., Andreeff, M., Konopleva, M.
(2008). Inhibition of mitochondrial metabolism by methyl-2-cyano-3,12-dioxooleana-1,9-diene-28-oate induces apoptotic or autophagic cell death in chronic myeloid leukemia cells. Molecular Cancer Therapeutics
7: 1130-1139
[Abstract][Full Text]
La Rosee, P., Holm-Eriksen, S., Konig, H., Hartel, N., Ernst, T., Debatin, J., Mueller, M. C., Erben, P., Binckebanck, A., Wunderle, L., Shou, Y., Dugan, M., Hehlmann, R., Ottmann, O. G., Hochhaus, A.
(2008). Phospho-CRKL monitoring for the assessment of BCR-ABL activity in imatinib-resistant chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia patients treated with nilotinib. haematol
93: 765-769
[Abstract][Full Text]
O'Hare, T., Eide, C. A., Tyner, J. W., Corbin, A. S., Wong, M. J., Buchanan, S., Holme, K., Jessen, K. A., Tang, C., Lewis, H. A., Romero, R. D., Burley, S. K., Deininger, M. W.
(2008). SGX393 inhibits the CML mutant Bcr-AblT315I and preempts in vitro resistance when combined with nilotinib or dasatinib. Proc. Natl. Acad. Sci. USA
105: 5507-5512
[Abstract][Full Text]
Kenealy, L. K., Christenson, C. B., Williams, C. B.
(2008). Current Therapies for Chronic Myeloid Leukemia. Journal of Pharmacy Practice
21: 116-125
[Abstract]
Ramirez, P., DiPersio, J. F.
(2008). Therapy Options in Imatinib Failures. The Oncologist
13: 424-434
[Abstract][Full Text]
Weisberg, E., Banerji, L., Wright, R. D., Barrett, R., Ray, A., Moreno, D., Catley, L., Jiang, J., Hall-Meyers, E., Sauveur-Michel, M., Stone, R., Galinsky, I., Fox, E., Kung, A. L., Griffin, J. D.
(2008). Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells. Blood
111: 3723-3734
[Abstract][Full Text]
Carayol, N., Katsoulidis, E., Sassano, A., Altman, J. K., Druker, B. J., Platanias, L. C.
(2008). Suppression of Programmed Cell Death 4 (PDCD4) Protein Expression by BCR-ABL-regulated Engagement of the mTOR/p70 S6 Kinase Pathway. J. Biol. Chem.
283: 8601-8610
[Abstract][Full Text]
Kaune, K. M., Baumgart, M., Gesk, S., Mitteldorf, C., Baesecke, J., Glass, B., Haase, D., Siebert, R., Ghadimi, B. M., Neumann, C., Emmert, S.
(2008). Bullous Sweet Syndrome in a Patient With t(9;22)(q34;q11)-Positive Chronic Myeloid Leukemia Treated With the Tyrosine Kinase Inhibitor Nilotinib: Interphase Cytogenetic Detection of BCR-ABL- Positive Lesional Cells. Arch Dermatol
144: 361-364
[Abstract][Full Text]
Laudadio, J., Deininger, M. W.N., Mauro, M. J., Druker, B. J., Press, R. D.
(2008). An Intron-Derived Insertion/Truncation Mutation in the BCR-ABL Kinase Domain in Chronic Myeloid Leukemia Patients Undergoing Kinase Inhibitor Therapy. J. Mol. Diagn.
10: 177-180
[Abstract][Full Text]
Fojo, T.
(2008). Commentary: Novel Therapies for Cancer: Why Dirty Might Be Better. The Oncologist
13: 277-283
[Full Text]
Copland, M., Pellicano, F., Richmond, L., Allan, E. K., Hamilton, A., Lee, F. Y., Weinmann, R., Holyoake, T. L.
(2008). BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Blood
111: 2843-2853
[Abstract][Full Text]
Mayerhofer, M., Gleixner, K. V., Mayerhofer, J., Hoermann, G., Jaeger, E., Aichberger, K. J., Ott, R. G., Greish, K., Nakamura, H., Derdak, S., Samorapoompichit, P., Pickl, W. F., Sexl, V., Esterbauer, H., Schwarzinger, I., Sillaber, C., Maeda, H., Valent, P.
(2008). Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia: a novel approach to overcome resistance against imatinib. Blood
111: 2200-2210
[Abstract][Full Text]
le Coutre, P., Ottmann, O. G., Giles, F., Kim, D.-W., Cortes, J., Gattermann, N., Apperley, J. F., Larson, R. A., Abruzzese, E., O'Brien, S. G., Kuliczkowski, K., Hochhaus, A., Mahon, F.-X., Saglio, G., Gobbi, M., Kwong, Y.-L., Baccarani, M., Hughes, T., Martinelli, G., Radich, J. P., Zheng, M., Shou, Y., Kantarjian, H.
(2008). Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood
111: 1834-1839
[Abstract][Full Text]
Garcia, A. A.
(2008). Small Molecules: Big Changes in the Cancer Treatment Paradigm. Journal of Pharmacy Practice
21: 17-35
[Abstract]
Yanada, M., Takeuchi, J., Sugiura, I., Akiyama, H., Usui, N., Yagasaki, F., Nishii, K., Ueda, Y., Takeuchi, M., Miyawaki, S., Maruta, A., Narimatsu, H., Miyazaki, Y., Ohtake, S., Jinnai, I., Matsuo, K., Naoe, T., Ohno, R., for the Japan Adult Leukemia Study Group,
(2008). Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy. haematol
93: 287-290
[Abstract][Full Text]
Marshall, H. M, Hammond, J. M
(2008). Treatment Options in Imatinib-Resistant Chronic Myelogenous Leukemia. The Annals of Pharmacotherapy
42: 259-264
[Abstract][Full Text]
Levine, R. L., Heaney, M.
(2008). New Advances in the Pathogenesis and Therapy of Essential Thrombocythemia. ASH Education Book
2008: 76-82
[Abstract][Full Text]
Wetzler, M.
(2008). Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: On Target to Improve Outcome. Am Soc Clin Oncol Ed Book
2008: 275-279
[Abstract][Full Text]
Rix, U., Hantschel, O., Durnberger, G., Remsing Rix, L. L., Planyavsky, M., Fernbach, N. V., Kaupe, I., Bennett, K. L., Valent, P., Colinge, J., Kocher, T., Superti-Furga, G.
(2007). Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood
110: 4055-4063
[Abstract][Full Text]
Cortes, J., Jabbour, E., Kantarjian, H., Yin, C. C., Shan, J., O'Brien, S., Garcia-Manero, G., Giles, F., Breeden, M., Reeves, N., Wierda, W. G., Jones, D.
(2007). Dynamics of BCR-ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors. Blood
110: 4005-4011
[Abstract][Full Text]
Kantarjian, H. M., Giles, F., Gattermann, N., Bhalla, K., Alimena, G., Palandri, F., Ossenkoppele, G. J., Nicolini, F.-E., O'Brien, S. G., Litzow, M., Bhatia, R., Cervantes, F., Haque, A., Shou, Y., Resta, D. J., Weitzman, A., Hochhaus, A., le Coutre, P.
(2007). Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood
110: 3540-3546
[Abstract][Full Text]
Press, R. D., Galderisi, C., Yang, R., Rempfer, C., Willis, S. G., Mauro, M. J., Druker, B. J., Deininger, M. W.N.
(2007). A Half-Log Increase in BCR-ABL RNA Predicts a Higher Risk of Relapse in Patients with Chronic Myeloid Leukemia with an Imatinib-Induced Complete Cytogenetic Response. Clin. Cancer Res.
13: 6136-6143
[Abstract][Full Text]
Goldman, J. M.
(2007). How I treat chronic myeloid leukemia in the imatinib era. Blood
110: 2828-2837
[Abstract][Full Text]
O'Hare, T., Eide, C. A., Deininger, M. W. N.
(2007). Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood
110: 2242-2249
[Abstract][Full Text]
Williams, R. T., den Besten, W., Sherr, C. J.
(2007). Cytokine-dependent imatinib resistance in mouse BCR-ABL+, Arf-null lymphoblastic leukemia. Genes Dev.
21: 2283-2287
[Abstract][Full Text]
Modugno, M., Casale, E., Soncini, C., Rosettani, P., Colombo, R., Lupi, R., Rusconi, L., Fancelli, D., Carpinelli, P., Cameron, A. D., Isacchi, A., Moll, J.
(2007). Crystal Structure of the T315I Abl Mutant in Complex with the Aurora Kinases Inhibitor PHA-739358. Cancer Res.
67: 7987-7990
[Abstract][Full Text]
Nicolini, F. E., Hayette, S., Corm, S., Bachy, E., Bories, D., Tulliez, M., Guilhot, F., Legros, L., Maloisel, F., Kiladjian, J.-J., Mahon, F.-X., Le, Q.-H., Michallet, M., Roche-Lestienne, C., Preudhomme, C.
(2007). Clinical outcome of 27 imatinib mesylate-resistant chronic myelogenous leukemia patients harboring a T315I BCR-ABL mutation. haematol
92: 1238-1241
[Abstract][Full Text]
Schiffer, C. A.
(2007). BCR-ABL Tyrosine Kinase Inhibitors for Chronic Myelogenous Leukemia. NEJM
357: 258-265
[Full Text]
Pfeifer, H., Wassmann, B., Pavlova, A., Wunderle, L., Oldenburg, J., Binckebanck, A., Lange, T., Hochhaus, A., Wystub, S., Bruck, P., Hoelzer, D., Ottmann, O. G.
(2007). Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood
110: 727-734
[Abstract][Full Text]
Carew, J. S., Nawrocki, S. T., Kahue, C. N., Zhang, H., Yang, C., Chung, L., Houghton, J. A., Huang, P., Giles, F. J., Cleveland, J. L.
(2007). Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl-mediated drug resistance. Blood
110: 313-322
[Abstract][Full Text]
Distler, J. H W, Distler, O.
(2007). Cardiotoxicity of imatinib mesylate: an extremely rare phenomenon or a major side effect?. Ann Rheum Dis
66: 836-836
[Full Text]
Guilhot, F.
(2007). No more transplantation in CML?. Blood
109: 4592-4592
[Full Text]
Ray, A., Cowan-Jacob, S. W., Manley, P. W., Mestan, J., Griffin, J. D.
(2007). Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study. Blood
109: 5011-5015
[Abstract][Full Text]
Hehlmann, R., Berger, U., Pfirrmann, M., Heimpel, H., Hochhaus, A., Hasford, J., Kolb, H.-J., Lahaye, T., Maywald, O., Reiter, A., Hossfeld, D. K., Huber, C., Loffler, H., Pralle, H., Queisser, W., Tobler, A., Nerl, C., Solenthaler, M., Goebeler, M. E., Griesshammer, M., Fischer, T., Kremers, S., Eimermacher, H., Pfreundschuh, M., Hirschmann, W.-D., Lechner, K., Wassmann, B., Falge, C., Kirchner, H. H., Gratwohl, A., for the Schweizerische Arbeitsgemeinschaft fur Kli,
(2007). Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood
109: 4686-4692
[Abstract][Full Text]
Jiang, X., Saw, K. M., Eaves, A., Eaves, C.
(2007). Instability of BCR-ABL Gene in Primary and Cultured Chronic Myeloid Leukemia Stem Cells. JNCI J Natl Cancer Inst
99: 680-693
[Abstract][Full Text]
Spinelli, O., Peruta, B., Tosi, M., Guerini, V., Salvi, A., Zanotti, M. C., Oldani, E., Grassi, A., Intermesoli, T., Mico, C., Rossi, G., Fabris, P., Lambertenghi-Deliliers, G., Angelucci, E., Barbui, T., Bassan, R., Rambaldi, A.
(2007). Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia. haematol
92: 612-618
[Abstract][Full Text]
Jorgensen, H. G., Allan, E. K., Jordanides, N. E., Mountford, J. C., Holyoake, T. L.
(2007). Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells. Blood
109: 4016-4019
[Abstract][Full Text]
Nguyen, T. K., Rahmani, M., Harada, H., Dent, P., Grant, S.
(2007). MEK1/2 inhibitors sensitize Bcr/Abl+ human leukemia cells to the dual Abl/Src inhibitor BMS-354/825. Blood
109: 4006-4015
[Abstract][Full Text]
Picard, S., Titier, K., Etienne, G., Teilhet, E., Ducint, D., Bernard, M.-A., Lassalle, R., Marit, G., Reiffers, J., Begaud, B., Moore, N., Molimard, M., Mahon, F.-X.
(2007). Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood
109: 3496-3499
[Abstract][Full Text]
Soverini, S., Iacobucci, I., Baccarani, M., Martinelli, G.
(2007). Targeted therapy and the T315I mutation in Philadelphia-positive leukemias. haematol
92: 437-439
[Full Text]
Perrotti, D., Neviani, P.
(2007). From mRNA Metabolism to Cancer Therapy: Chronic Myelogenous Leukemia Shows the Way. Clin. Cancer Res.
13: 1638-1642
[Abstract][Full Text]
Rowe, J. M.
(2007). Closing the gap in CML. Blood
109: 2271-2271
[Full Text]
Roberts, K. G., Odell, A. F., Byrnes, E. M., Baleato, R. M., Griffith, R., Lyons, A. B., Ashman, L. K.
(2007). Resistance to c-KIT kinase inhibitors conferred by V654A mutation. Molecular Cancer Therapeutics
6: 1159-1166
[Abstract][Full Text]
Weisberg, E., Catley, L., Wright, R. D., Moreno, D., Banerji, L., Ray, A., Manley, P. W., Mestan, J., Fabbro, D., Jiang, J., Hall-Meyers, E., Callahan, L., DellaGatta, J. L., Kung, A. L., Griffin, J. D.
(2007). Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood
109: 2112-2120
[Abstract][Full Text]
Wang, Y., Cai, D., Brendel, C., Barett, C., Erben, P., Manley, P. W., Hochhaus, A., Neubauer, A., Burchert, A.
(2007). Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation. Blood
109: 2147-2155
[Abstract][Full Text]
Bozulic, L., Morin, P. J., Hunter, T., Hemmings, B. A.
(2007). Meeting Report: Targeting the Kinome--20 Years of Tyrosine Kinase Inhibitor Research in Basel. Sci Signal
2007: pe8-pe8
[Abstract][Full Text]
Kantarjian, H. M., Giles, F., Quintas-Cardama, A., Cortes, J.
(2007). Important Therapeutic Targets in Chronic Myelogenous Leukemia. Clin. Cancer Res.
13: 1089-1097
[Abstract][Full Text]
Lerma, E. I., Nguyen, V.-A., Wang, T., Tipping, A., Melo, J. V., Kufe, D., Austin, D. J., Deisseroth, A.
(2007). Novel compounds with antiproliferative activity against imatinib-resistant cell lines. Molecular Cancer Therapeutics
6: 655-666
[Abstract][Full Text]
Martinelli, G., Soverini, S., Iacobucci, I., Baccarani, M.
(2007). MK-0457: a light at the end of the tunnel?. Blood
109: 396-397
[Full Text]
Giles, F. J., Cortes, J., Jones, D., Bergstrom, D., Kantarjian, H., Freedman, S. J.
(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
109: 500-502
[Abstract][Full Text]
Radich, J. P.
(2007). The Biology of CML Blast Crisis. ASH Education Book
2007: 384-391
[Abstract][Full Text]
Thomas, D. A.
(2007). Philadelphia Chromosome Positive Acute Lymphocytic Leukemia: A New Era of Challenges. ASH Education Book
2007: 435-443
[Abstract][Full Text]
Kantarjian, H. M., Talpaz, M., Giles, F., O'Brien, S., Cortes, J.
(2006). New Insights into the Pathophysiology of Chronic Myeloid Leukemia and Imatinib Resistance. ANN INTERN MED
145: 913-923
[Abstract][Full Text]
Soverini, S., Colarossi, S., Gnani, A., Rosti, G., Castagnetti, F., Poerio, A., Iacobucci, I., Amabile, M., Abruzzese, E., Orlandi, E., Radaelli, F., Ciccone, F., Tiribelli, M., di Lorenzo, R., Caracciolo, C., Izzo, B., Pane, F., Saglio, G., Baccarani, M., Martinelli, G., on behalf of the GIMEMA Working Party on Chronic M,
(2006). Contribution of ABL Kinase Domain Mutations to Imatinib Resistance in Different Subsets of Philadelphia-Positive Patients: By the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin. Cancer Res.
12: 7374-7379
[Abstract][Full Text]
Druker, B. J., Guilhot, F., O'Brien, S. G., Gathmann, I., Kantarjian, H., Gattermann, N., Deininger, M. W.N., Silver, R. T., Goldman, J. M., Stone, R. M., Cervantes, F., Hochhaus, A., Powell, B. L., Gabrilove, J. L., Rousselot, P., Reiffers, J., Cornelissen, J. J., Hughes, T., Agis, H., Fischer, T., Verhoef, G., Shepherd, J., Saglio, G., Gratwohl, A., Nielsen, J. L., Radich, J. P., Simonsson, B., Taylor, K., Baccarani, M., So, C., Letvak, L., Larson, R. A., the IRIS Investigators,
(2006). Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia. NEJM
355: 2408-2417
[Abstract][Full Text]
Fausel, C. A.
(2006). Novel treatment strategies for chronic myeloid leukemia.. Am J Health Syst Pharm
63: S15-S20
[Abstract][Full Text]
Talpaz, M., Shah, N. P., Kantarjian, H., Donato, N., Nicoll, J., Paquette, R., Cortes, J., O'Brien, S., Nicaise, C., Bleickardt, E., Blackwood-Chirchir, M. A., Iyer, V., Chen, T.-T., Huang, F., Decillis, A. P., Sawyers, C. L.
(2006). Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias.. NEJM
354: 2531-2541
[Abstract][Full Text]
Druker, B. J.
(2006). Circumventing resistance to kinase-inhibitor therapy.. NEJM
354: 2594-2596
[Full Text]
Mauro, M. J.
(2006). Defining and Managing Imatinib Resistance. ASH Education Book
2006: 219-225
[Abstract][Full Text]
Previous
