Current Treatment Options in Oncology

, Volume 8, Issue 4, pp 287–295 | Cite as

Mutational Analysis and Overcoming Imatinib Resistance in Chronic Myeloid Leukemia with Novel Tyrosine Kinase Inhibitors

Acute Leukemia


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: *Of importance **Of major importance

  1. 1.
    Peng B, Hayes M, Resta D, et al.: Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol 2004; 22(5):935–942PubMedCrossRefGoogle Scholar
  2. 2.
    Druker BJ, Talpaz M, Resta DJ, et al.: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344(14):1031–1037PubMedCrossRefGoogle Scholar
  3. 3.**
    Druker BJ, Guilhot F, O’Brien SG, et al.: Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355:2408–2417PubMedCrossRefGoogle Scholar
  4. 4.
    Kantarjian H, Talpaz M, O’Brien S, et al.: High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood 2004; 103(8):2873–2878PubMedCrossRefGoogle Scholar
  5. 5.
    Druker BJ, Kantarjian HM, Talpaz M, et al.: A Phase I study of Gleevec (Imatinib Mesylate) administered concomitantly with cytosine arabinoside (Ara-C) in patients with Philadelphia positive chronic myeloid leukemia (CML). Blood 2001; 98:845aGoogle Scholar
  6. 6.
    O’Dwyer ME, Mauro MJ, Kuyl J, et al.: Preliminary evaluation of the combination of Imatinib mesylate (Gleevec) in combination with low dose Interferon-alpha for the treatment of chronic phase CML. Blood 2001; 98(11):846aGoogle Scholar
  7. 7.
    Mauro MJ, O’Dwyer ME, Stone RM, et al.: Preliminary evaluation of the combination of imatinib mesylate (Gleevec) with low dose Ara-C as initial therapy for newly diagnosed chronic phase CML. Blood 2002; 100(11):165aGoogle Scholar
  8. 8.
    Gardembas M, Rousselot P, Tulliez M, et al.: Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase. Blood 2003; 102(13):4298–4305PubMedCrossRefGoogle Scholar
  9. 9.
    Gorre ME, Mohammed M, Ellwood K, et al.: Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001; 293:876–888PubMedCrossRefGoogle Scholar
  10. 10.
    Hughes T, Deininger M, Hochhaus A, et al.: Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006; 108:28–37PubMedCrossRefGoogle Scholar
  11. 11.
    Deininger M, Buchdunger E, Druker BJ: The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005; 105:2640–2653PubMedCrossRefGoogle Scholar
  12. 12.
    Schindler T, Bornmann W, Pellicena P, et al.: Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 2000; 289(5486):1938–1942PubMedCrossRefGoogle Scholar
  13. 13.
    Hochhaus A, Kreil S, Corbin AS, et al.: Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002; 16:2190–2196PubMedCrossRefGoogle Scholar
  14. 14.
    Donato NJ, Wu JY, Stapley J, et al.: BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 2003; 101:690–698PubMedCrossRefGoogle Scholar
  15. 15.*
    Deborah L, White DL, Verity A, et al.: OCT-1–mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood 2006; 108(2):697–704CrossRefGoogle Scholar
  16. 16.
    Willis SG, Lange T, Demehri S, et al.: High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood 2005;106:2128–2137PubMedCrossRefGoogle Scholar
  17. 17.
    National Comprehensive Cancer Network Chronic Myelogenous Leukemia Clinical Practice Guidelines in Oncology, v.2.2008. Accessed August 1, 2007
  18. 18.**
    Baccarani M, Saglio G, Goldman J, et al.: Evolving concepts in the management of chronic myeloid leukemia. Recommendations from an expert panel on behalf of the European Leukemia net. Blood 2006; 108(6):1809–1820PubMedCrossRefGoogle Scholar
  19. 19.*
    Talpaz M, Shah NP, Kantarjian H, et al.: Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006; 354:2531–2541PubMedCrossRefGoogle Scholar
  20. 20.*
    Kantarjian H, Giles F, Wunderle L, et al.: Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006; 354:2542–2551PubMedCrossRefGoogle Scholar
  21. 21.
    Baccarani HM, Kantarjian H, Apperley JF, et al.: Efficacy of dasatinib (Sprycel) in patients with chronic phase chronic myeloid leukemia (CP-CML) resistant or intolerant to imatinib: updated results of the CA180013 ‘START-C’ phase II study. Blood (ASH Annual Meeting Abstracts) 2006; 108:164aGoogle Scholar
  22. 22.**
    Hochhaus A, Kantarjian HM, Baccarani M, et al.: Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 2007;109:2303–2309PubMedCrossRefGoogle Scholar
  23. 23.
    Guilhot F, Apperley J, Facon T, et al.: Dasatinib induces durable cytogenetic responses in patients with chronic-phase CML with resistance or intolerance to imatinib: updated results of the CA180013 (START-C) trial. European Hematology Association Proceedings 2007, Abstract #358Google Scholar
  24. 24.
    Rosti G, le Coutre P, Bhalla K, et al.: A phase II study of nilotinib administered to imatinib resistant and intolerant patients with chronic myelogenous leukemia (CML) in chronic phase (CP). ASCO 2007, #7007 (Abstract)Google Scholar
  25. 25.**
    Kantarjian HM, Giles F, Gattermann N, et al.: 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 2007, 110(10):3540–3546Google Scholar
  26. 26.**
    Kantarjian H, Pasquini R, Hamerschlak N, et al.: Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood 2007; 109(12):5143–5150PubMedCrossRefGoogle Scholar
  27. 27.
    Hochhaus A, Kim DW, Rousselot P, et al.: Dasatinib (SPRYCEL) 50 mg or 70 mg BID versus 100 mg or 140 mg QD in patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant or intolerant to imatinib: results of the CA180-034 study. Blood (ASH Annual Meeting Abstracts) 2006; 108:166Google Scholar
  28. 28.
    Giles F, Cortes J, Bergstrom DA, et al.: MK-0457, a novel aurora kinase and BCR-ABL inhibitor, is active against BCR-ABL T315I mutant chronic myelogenous leukemia (CML). Blood (ASH Annual Meeting Abstracts) 2006; 108:163Google Scholar
  29. 29.
    Cortes J, Kantarjian H, Baccarani M, et al.: A Phase 1/2 Study of SKI-606, a dual inhibitor of Src and Abl kinases, in adult patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) relapsed, refractory or intolerant of imatinib. Blood (ASH Annual Meeting Abstracts) 2006; 108:168Google Scholar
  30. 30.
    Yokota A, Kimura S, Masuda S, et al.: 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 2007; 109(1):306–314PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2007

Authors and Affiliations

  1. 1.Center for Hematologic MalignanciesOregon Health & Science UniversityPortlandUSA

Personalised recommendations