Access the full text.
Sign up today, get DeepDyve free for 14 days.
M. Anafi, A. Gazit, Amos Zehavi, Y. Ben-Neriah, A. Levitzki (1993)
Tyrphostin-induced inhibition of p210bcr-abl tyrosine kinase activity induces K562 to differentiate.Blood, 82 12
J. Goldman, J. Melo (2001)
Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia.The New England journal of medicine, 344 14
P.J. Fialkow (1981)
Evidence for a multistep origin of chronic myeloid leukemiaBlood, 58
B. Druker, C. Sawyers, H. Kantarjian, D. Resta, Sofia Reese, J. Ford, R. Capdeville, M. Talpaz (2001)
Activity 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 chromosome.The New England journal of medicine, 344 14
R. Sprengel, J. Bissonnette, W. Kaufmann, D. Pribnow, T. Neelands, T. Storck, M. Baetscher, Jasna Jerecic, J. Maylie, H. Knaus, P. Seeburg, J. Adelman (2000)
Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.Science, 289 5486
J.M. Goldman, J.V. Melo (2001)
Targeting the BCR-ABL kinase in chronic myeloid leukemiaN Engl J Med, 344
J. Goldman, B. Druker (2001)
Chronic myeloid leukemia: current treatment options.Blood, 98 7
Kristen Smith, R. Yacobi, R. Etten (2003)
Autoinhibition of Bcr-Abl through Its SH3 DomainMolecular Cell, 12
K.M. Shannon (2002)
Resistance in the land of molecular therapeuticsCancer Cell, 2
M. Gorre, M. Mohammed, K. Ellwood, N. Hsu, R. Paquette, P. Rao, C. Sawyers (2001)
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or AmplificationScience, 293
E. Buchdunger, C. Cioffi, N. Law, D. Stover, Sayuri Ohno-Jones, B. Druker, N. Lydon (2000)
Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors.The Journal of pharmacology and experimental therapeutics, 295 1
B. Druker, N. Lydon (2000)
Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia.The Journal of clinical investigation, 105 1
G. Demetri, M. Mehren, C. Blanke, A. Abbeele, B. Eisenberg, P. Roberts, M. Heinrich, D. Tuveson, S. Singer, M. Janicek, J. Fletcher, S. Silverman, S. Silberman, R. Capdeville, B. Kiese, B. Peng, S. Dimitrijević, B. Druker, C. Corless, C. Fletcher, H. Joensuu (2002)
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.The New England journal of medicine, 347 7
J. Melo (1996)
The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype.Blood, 88 7
P.C. Nowell, D.A. Hungerford (1960)
A minute chromosome in human chronic granulocytic leukemia [letter]Science, 132
K. Okuda, E. Weisberg, D. Gilliland, J. Griffin (2001)
ARG tyrosine kinase activity is inhibited by STI571.Blood, 97 8
H. Kantarjian, C. Sawyers, A. Hochhaus, F. Guilhot, C. Schiffer, C. Gambacorti-Passerini, D. Niederwieser, D. Resta, R. Capdeville, U. Zoellner, M. Talpaz, B. Druker, J. Goldman, S. O’Brien, N. Russell, T. Fischer, O. Ottmann, P. Cony-Makhoul, T. Facon, R. Stone, Carole Miller, M. Tallman, R. Brown, M. Schuster, T. Loughran, A. Gratwohl, F. Mandelli, G. Saglio, M. Lazzarino, D. Russo, M. Baccarani, E. Morra (2002)
Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia.The New England journal of medicine, 346 9
S. O’Brien, F. Guilhot, R. Larson, I. Gathmann, M. Baccarani, F. Cervantes, J. Cornelissen, T. Fischer, A. Hochhaus, T. Hughes, K. Lechner, J. Nielsen, P. Rousselot, J. Reiffers, G. Saglio, J. Shepherd, B. Simonsson, A. Gratwohl, J. Goldman, H. Kantarjian, K. Taylor, G. Verhoef, A. Bolton, R. Capdeville, B. Druker (2003)
Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.The New England journal of medicine, 348 11
G. Daley, R. Etten, D. Baltimore (1990)
Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome.Science, 247 4944
M. Okabe, Yoshimasa Uehara, Takuto Miyagishima, Toshiyuki Itaya, Masanori Tanaka, Yasuyuki Kunieda, Mitsutoshi Kurosawa, Tamotsu Miyazaki (1992)
Effect of herbimycin A, an antagonist of tyrosine kinase, on bcr/abl oncoprotein-associated cell proliferations: abrogative effect on the transformation of murine hematopoietic cells by transfection of a retroviral vector expressing oncoprotein P210bcr/abl and preferential inhibition on Ph1-positiveBlood, 80 5
J. Cortes, F. Giles, S. O'brien, D. Thomas, G. Garcia-Manero, M. Rios, S. Faderl, S. Verstovsek, A. Ferrajoli, E. Freireich, M. Talpaz, H. Kantarjian (2003)
Result of high-dose imatinib mesylate in patients with Philadelphia chromosome-positive chronic myeloid leukemia after failure of interferon-alpha.Blood, 102 1
M. Deininger, J. Goldman, J. Melo (2000)
The molecular biology of chronic myeloid leukemia.Blood, 96 10
K. Lyseng-Williamson, B. Jarvis (2001)
ImatinibDrugs, 61
H. Kantarjian, M. Talpaz, S. O'brien, F. Giles, G. Garcia-Manero, S. Faderl, D. Thomas, J. Shan, M. Rios, J. Cortes (2003)
Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia.Blood, 101 2
M. Sattler, J. Griffin (2003)
Molecular mechanisms of transformation by the BCR-ABL oncogene.Seminars in hematology, 40 2 Suppl 2
M. Talpaz, R. Silver, B. Druker, J. Goldman, C. Gambacorti-Passerini, F. Guilhot, C. Schiffer, T. Fischer, M. Deininger, A. Lennard, A. Hochhaus, O. Ottmann, A. Gratwohl, M. Baccarani, R. Stone, S. Tura, F. Mahon, Sofia Fernandes-Reese, I. Gathmann, R. Capdeville, H. Kantarjian, C. Sawyers (2002)
Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study.Blood, 99 6
(2001)
Chronic myeloid leukaemia. STI 571 magnifies the therapeutic dilemma.
T.P. Hughes, J. Kaeda, S. Branford (2003)
On behalf of the IRIS study group. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed patients with chronic myeloid leukemiaNew Engl J Med, 349
J. Cools, D. DeAngelo, J. Gotlib, E. Stover, R. Legare, J. Cortes, J. Kutok, Jennifer Clark, I. Galinsky, J. Griffin, N. Cross, A. Tefferi, J. Malone, R. Alam, S. Schrier, J. Schmid, M. Rose, P. Vandenberghe, G. Verhoef, M. Boogaerts, I. Wlodarska, H. Kantarjian, P. Marynen, S. Coutre, R. Stone, D. Gilliland (2003)
A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome.The New England journal of medicine, 348 13
E. Weisberg, J. Griffin (2000)
Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABL–transformed hematopoietic cell linesBlood, 95
T. Lugo, A. Pendergast, A. Muller, O. Witte (1990)
Tyrosine kinase activity and transformation potency of bcr-abl oncogene products.Science, 247 4946
T. Hughes, J. Kaeda, S. Branford, Z. Rudzki, A. Hochhaus, M. Hensley, I. Gathmann, A. Bolton, Iris Hoomissen, J. Goldman, J. Radich (2003)
Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia.The New England journal of medicine, 349 15
K. Shannon (2002)
Resistance in the land of molecular cancer therapeutics.Cancer cell, 2 2
F. Mahon, M. Deininger, B. Schultheis, J. Chabrol, J. Reiffers, J. Goldman, J. Melo (2000)
Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance.Blood, 96 3
P. Fialkow, P. Martin, V. Najfeld, G. Penfold, R. Jacobson, J. Hansen (1981)
Evidence for a multistep pathogenesis of chronic myelogenous leukemia.Blood, 58 1
B. Druker, M. Talpaz, D. Resta, B. Peng, E. Buchdunger, J. Ford, N. Lydon, H. Kantarjian, R. Capdeville, Sayuri Ohno-Jones, C. Sawyers (2001)
Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.The New England journal of medicine, 344 14
J. Goldman (2000)
Tyrosine-kinase inhibition in treatment of chronic myeloid leukaemiaThe Lancet, 355
P. Coutre, Elena Tassi, M. Varella-Garcia, Rossella Barni, L. Mologni, G. Cabrita, E. Marchesi, R. Supino, C. Gambacorti-Passerini (2000)
Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification.Blood, 95 5
J. Apperley, M. Gardembas, J. Melo, R. Russell‐Jones, B. Bain, E. Baxter, A. Chase, J. Chessells, Marie Colombat, C. Dearden, S. Dimitrijević, F. Mahon, D. Marin, Z. Nikolova, E. Olavarría, S. Silberman, B. Schultheis, N. Cross, J. Goldman (2002)
Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.The New England journal of medicine, 347 7
C. Roche-Lestienne, V. Soenen-Cornu, Nathalie Grardel-Duflos, J. Laï, N. Philippe, T. Facon, P. Fenaux, C. Preudhomme (2002)
Several 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 treatment.Blood, 100 3
Ravi Bhatia, H. Munthe, Catherine Verfaillie (1998)
Tyrphostin AG957, a tyrosine kinase inhibitor with anti-BCR/ABL tyrosine kinase activity restores β1 integrin-mediated adhesion and inhibitory signaling in chronic myelogenous leukemia hematopoietic progenitorsLeukemia, 12
T. Mughal, A. Yong, Richard Szydlo, F. Dazzi, E. Olavarría, F. Rhee, J. Kaeda, N. Cross, C. Craddock, E. Kanfer, J. Apperley, J. Goldman (2001)
Molecular studies in patients with chronic myeloid leukaemia in remission 5 years after allogeneic stem cell transplant define the risk of subsequent relapseBritish Journal of Haematology, 115
B. Druker, S. Tamura, E. Buchdunger, S. Ohno, G. Segal, S. Fanning, J. Zimmermann, N. Lydon (1996)
Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cellsNature Medicine, 2
Carlo Gambacorti-Passerini, Rossella Barni, P. Coutre, Massimo Zucchetti, Gonçalo Cabrita, L. Cleris, Francesca Rossi, E. Gianazza, Josef, Brueggen, Robert Cozens, Pietro Pioltelli, E. Pogliani, Gianmarco Corneo, F. Formelli, Maurizio D'Incalci (2000)
Role of (cid:1) 1 Acid Glycoprotein in the In Vivo Resistance of Human BCR-ABL + Leukemic Cells to the Abl Inhibitor STI571
N. Shah, J. Nicoll, B. Nagar, M. Gorre, R. Paquette, J. Kuriyan, C. Sawyers (2002)
Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia.Cancer cell, 2 2
P. Nowell, D. Hungerford, P. Nowell (1960)
A minute chromosome in human chronic granulocytic leukemiaScience, 132
M. Lichtman, J. Spivak, L. Boxer, S. Shattil, E. Henderson (2000)
Commentary on and reprint of Nowell PC, Hungerford DA, A minute chromosome in human chronic granulocytic leukemia, in Science (1960) 132:1497
N. Bubnoff, F. Schneller, C. Peschel, J. Duyster (2002)
BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective studyThe Lancet, 359
J. Goldman, J. Apperley, L. Jones, R. Marcus, A. Goolden, R. Batchelor, G. Hale, H. Waldmann, C. Reid, J. Hows, E. Gordon-Smith, D. Catovsky, D. Galton (1986)
Bone marrow transplantation for patients with chronic myeloid leukemia.The New England journal of medicine, 314 4
T.I. Mughal, A. Yong, R.M. Szydlo (2001)
The probability of long-term leukaemia free survival for patients in molecular remission 5 years after allogeneic stem cell transplantation for chronic myeloid leukaemia in chronic phaseBr J Haematol, 115
C. Sawyers, A. Hochhaus, E. Feldman, J. Goldman, Carole Miller, O. Ottmann, C. Schiffer, M. Talpaz, F. Guilhot, M. Deininger, T. Fischer, S. O’Brien, R. Stone, C. Gambacorti-Passerini, N. Russell, J. Reiffers, T. Shea, B. Chapuis, S. Coutre, S. Tura, E. Morra, R. Larson, A. Saven, C. Peschel, A. Gratwohl, F. Mandelli, M. Ben-Am, I. Gathmann, R. Capdeville, R. Paquette, B. Druker (2002)
Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study.Blood, 99 10
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that results from an acquired genetic change in a single pluripotential hemopoietic stem cell. The molecular hallmark of CML is the BCR-ABL gene rearrangement, which typically is generated by the Philadelphia (Ph) chromosome. The Ph chromosome abnormality arises as a result of a mutated stem cell acquiring a balanced reciprocal translocation involving chromosomes 9 and 22. The chimeric BCR-ABL gene encodes an oncoprotein, termed p210BCR-ABL protein, which has an enhanced and deregulated tyrosine kinase activity. It is generally regarded as the principal molecular cause of the initial indolent stage (chronic phase) of CML and further proof for this notion came from the remarkable activity of the Abl kinase inhibitor, imatinib mesylate (formerly STI 571). Imatinib mesylate targets the autophosphorylation of the Abl kinase specifically and is not only effective in the majority of patients, its also relatively free of major adverse effects. Current experience suggests hematological responses in over 95% of patients in the chronic phase of CML, with about 70% achieving a major cytogenic response. The drug is only able to achieve complete molecular responses in a minority of patients and so may not affect molecular cure. It is noteworthy that patients in the more advanced phases of CML, which involves additional clonal events, also respond to imatinib mesylate but have a high incidence of treatment resistance and relapse.
American Journal of Cancer – Springer Journals
Published: Aug 10, 2012
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.