| Hanyang Med Rev. 2012 May;32(2):103-111. Korean. Published online May 25, 2012. https://doi.org/10.7599/hmr.2012.32.2.103 | |
| Copyright © 2012 Hanyang University School of Medicine | |
Hawk Kim, M.D., Ph.D.
| |
| Division of Hematology-Oncology, University of Ulsan College of Medicine, Ulsan, Korea. | |
| Corresponding author (
)
| |
| Received February 25, 2012; Accepted April 19, 2012. | |
|
Abstract
| |
|
Chronic myeloid leukemia (CML) is a malignant disease induced by the oncogenic signal of the BCRABL transcript resulting from the translocation between chromosome 9 and 22, t (9:22). This genetic alteration evoked the development of imatinib, a tyrosine kinas inhibitor (TKI) targeting BCR-ABL tyrosine kinase. This drug showed higher activity with durable response compared with conventional interferon therapy and became a standard therapy for newly diagnosed CML patients. Dasatinib and nilotinib, the next generation TKIs are used for patients with chronic phase CML as first line therapy as well after finding that these drugs exert faster and deeper response than imatinib. Resistance and intolerance to BCR-ABL TKIs are the obstacles to managing patients. Substantial new drugs are developed for targeting mutations resistant to BCR-ABL TKIs. More concern is paid to long-term management of patients showing complications when taking these drugs, and eventually stopping drugs in selected patient populations are being evaluated. |
|
Keywords: Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Imatinib; Dasatinib; Nilotinib |
|
|
References
|
| 1. | Reilly JT. Chronic Idiopathic Myelofibrosis. In: Melo JV, Goldman JM, editors. Hematologic malignancies : myeloproliferative disorders. 1st ed. Berlin; New York: Springer; 2007. pp. 252-276. |
| 2. | Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 1990;247:824–830. 
|
| 3. | Kelliher MA, McLaughlin J, Witte ON, Rosenberg N. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci U S A 1990;87:6649–6653.
|
| 4. | Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 1990;247:1079–1082.
|
| 5. | Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996;2:561–566.
|
| 6. | Kitano T, Ateshian GA, Mow VC, Kadoya Y, Yamano Y. Constituents and pH changes in protein rich hyaluronan solution affect the biotribological properties of artificial articular joints. J Biomech 2001;34:1031–1037.
|
| 7. | O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994–1004. |
| 8. | Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002;346:645–652.
|
| 9. | Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27:6041–6051.
|
| 10. | de Lavallade H, Apperley JF, Khorashad JS, Milojkovic D, Reid AG, Bua M, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 2008;26:3358–3363.
|
| 11. | Hughes TP, Hochhaus A, Branford S, Muller MC, Kaeda JS, Foroni L, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 2010;116:3758–3765.
|
| 12. | Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood 1984;63:789–799.
|
| 13. | Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, et al. Writing Committee for the Collaborative CML Prognostic Factors Project Group. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst 1998;90:850–858.
|
| 14. | Deininger M, O'Brien SG, Guilhot F. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood 2009;114:1126. |
| 15. | Cortes JE, Baccarani M, Guilhot F, Druker BJ, Branford S, Kim DW, et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol 2010;28:424–430.
|
| 16. | Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Muller MC, Pletsch N, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. J Clin Oncol 2011;29:1634–1642.
|
| 17. | Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 2010;363:2511–2521.
|
| 18. | Cortes JE, Jones D, O'Brien S, Jabbour E, Ravandi F, Koller C, et al. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol 2010;28:398–404.
|
| 19. | Cortes JE, Jones D, O'Brien S, Jabbour E, Konopleva M, Ferrajoli A, et al. Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol 2010;28:392–397.
|
| 20. | Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, et al. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood 2009;114:4933–4938.
|
| 21. | Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260–2270.
|
| 22. | Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251–2259.
|
| 23. | Kantarjian HM, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol 2011;12:841–851.
|
| 24. | Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 2012;119:1123–1129.
|
| 25. | Gambacorti-Passerini C, Kim DW, Kantarjian HM. An ongoing phase 3 study of bosutinib (SKI-606) versus imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia. Blood 2010;116:208. |
| 26. | Marcucci G, Perrotti D, Caligiuri MA. Understanding the molecular basis of imatinib mesylate therapy in chronic myelogenous leukemia and the related mechanisms of resistance. Commentary re: A. N. Mohamed et al., The effect of imatinib mesylate on patients with Philadelphia chromosome-positive chronic myeloid leukemia with secondary chromosomal aberrations. Clin. Cancer Res., 9: 1333-1337, 2003. Clin Cancer Res 2003;9:1248–1252.
|
| 27. | von Bubnoff N, Schneller F, Peschel C, Duyster J. BCRABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet 2002;359:487–491.
|
| 28. | Shah NP, Nicoll JM, Nagar B, Gorre ME, Paquette RL, Kuriyan J, et al. 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 2002;2:117–125.
|
| 29. | Hochhaus A, Kreil S, Corbin AS, La Rosee P, Muller MC, Lahaye T, et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002;16:2190–2196.
|
| 30. | Branford S, Rudzki Z, Walsh S, Grigg A, Arthur C, Taylor K, et al. 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 2002;99:3472–3475.
|
| 31. | Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293:876–880.
|
| 32. | Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006;354:2531–2541.
|
| 33. | Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006;354:2542–2551.
|
| 34. | Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305:399–401.
|
| 35. | O'Hare T, Walters DK, Stoffregen EP, Jia T, Manley PW, Mestan J, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 2005;65:4500–4505. |
| 36. | Cortes J, Talpaz M, Bixby D. A Phase 1 Trial of Oral Ponatinib (AP24534) In Patients with Refractory Chronic Myelogenous Leukemia (CML) and Other Hematologic Malignancies: Emerging Safety and Clinical Response Findings. Blood 2010;116:210.
|
| 37. | Cortes JE, Kim D-W, Pinilla-Ibarz J. Initial Findings From the PACE Trial: A Pivotal Phase 2 Study of Ponatinib in Patients with CML and Ph+ ALL Resistant or Intolerant to Dasatinib or Nilotinib, or with the T315I Mutation. Blood 2011;118:109.
|
| 38. | Eide CA, Adrian LT, Tyner JW, Mac Partlin M, Anderson DJ, Wise SC, et al. The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCRABLT315I and exhibits a narrow resistance profile. Cancer Res 2011;71:3189–3195.
|
| 39. | Chan WW, Wise SC, Kaufman MD, Ahn YM, Ensinger CL, Haack T, et al. Conformational control inhibition of the BCRABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036. Cancer Cell 2011;19:556–568.
|
| 40. | Cortes-Franco J, Raghunadharao D, Parikh P, et al. Safety and efficacy of subcutaneous-administered omacetaxine mepesuccinate in imatinib-resistant chronic myeloid leukemia (CML) patients who harbor the Bcr-Abl T315I mutation results of an ongoing multicenter phase 2/3 study. Blood 2009;114:644. |
| 41. | Klag T, Hartel N, Erben P, Schwaab J, Schnetzke U, Schenk T, et al. Omacetaxine mepesuccinate prevents cytokinedependent resistance to nilotinib in vitro: potential role of the common beta-subunit c of cytokine receptors. Leukemia. Forthcoming 2012.
|
| 42. | Coude MM, Luycx O, Cariou ME, Maarek O, Dombret H, Cayuela JM, et al. Undetectable molecular residual disease after omacetaxine and nilotinib combination therapy in an imatinib-resistant chronic myeloid leukaemia patient harbouring the BCR-ABL1 T315I gatekeeper mutation. Br J Haematol 2012;157:407–410.
|
| 43. | Nicolini FE, Chomel JC, Roy L, Legros L, Chabane K, Ducastelle S, et al. The durable clearance of the T315I BCRABL mutated clone in chronic phase chronic myelogenous leukemia patients on omacetaxine allows tyrosine kinase inhibitor rechallenge. Clin Lymphoma Myeloma Leuk 2010;10:394–399.
|
| 44. | Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11:1029–1035.
|
Development of Tyrosine Kinase Inhibitor in Chronic Myeloid Leukemia
