medigraphic.com
ISSN 0016-3813 (Impreso)

2013, Número 6

<< Anterior Siguiente >>

Gac Med Mex 2013; 149 (6)


Inhibidores de cinasas de tirosina (ICT): la nueva revolución en el tratamiento de la leucemia mieloide crónica (LMC)

Avilés-Vázquez S, Chávez-González A, Mayani H

Idioma: Español
Referencias bibliográficas: 55
Paginas: 646-654
Archivo PDF: 286.66 Kb.


RESUMEN

La LMC es una neoplasia mieloproliferativa clonal, asociada a la translocación recíproca t(9,22)(q34:q11), conocida como cromosoma Filadelfia (Ph). De esta translocación se genera un gen quimérico (bcr-abl) que es traducido en la proteína BCR-ABL, cuya actividad de cinasa de tirosina se presenta de manera constitutiva, causando diversas alteraciones funcionales en la célula. El conocimiento estructural y funcional de la proteína BCR-ABL ha permitido el desarrollo de moléculas capaces de inhibir, de manera selectiva, su actividad de cinasa. Cinco de dichas moléculas ya han sido empleadas en la clínica para el tratamiento de pacientes con LMC Ph+. Los resultados obtenidos han sido muy buenos, pues han conseguido tasas de remisión nunca antes vistas con ningún otro fármaco y han brindado a los pacientes una buena calidad de vida. Sin embargo, existen problemas, aún no resueltos, relacionados con la acción de dichos inhibidores. Se ha visto que, por un lado, una proporción significativa de pacientes desarrolla resistencia a estos fármacos y, por otro, estas moléculas pueden inhibir la proliferación de las células leucémicas, pero no son capaces de eliminar las células troncales leucémicas. Lo anterior plantea retos importantes para el futuro inmediato.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Faderl S, Talpaz M, Estrov Z, et al. Chronic myelogenous leukemia: biology and therapy. Ann Intern Med. 1999;131:207-19.

  2. Faderl S, Talpaz M, Estrov Z, et al. The Biology of Chronic Myeloid Leukemia. N Engl J Med. 1999;341:164-72.

  3. Chavez-González MA, Ayala-Sanchéz M Mayani, H. La leucemia mieloide crónica en el siglo XXI: biología y tratamiento. Rev Invest Clin. 2009;61(3):221-32.

  4. Druker B. Chronic Myelogenous Leukemia. En: Runge MS, Patterson C. Principles of Molecular Medicine. 2.a ed. Totowa, NJ: Humana Press, Inc.; 2006. p. 789-93.

  5. Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinaseactivity and transformation potency of bcr-abl oncogene products. Science. 1990;247:1079-108.

  6. Petzer AL, Gunsilius E. Hematopoietic stem cells in chronic myeloid leukemia. Arch Med Res. 2003;34:496-506.

  7. Marley SB, Gordon MY. Chronic myeloid leukemia: stem cell derived but progenitor cell driven. Clin Science. 2005;109:13-25.

  8. Mayani H, Flores-Figueroa E, Chavez-Gonzalez A. In vitro biology of human myeloid leukemia. Leuk Res. 2009;33:624-37.

  9. Goldman JM, Daley GQ. Chronic Myeloid Leukemia – A Brief History. En: Melo JV, Goldman J. Hematologic Malignancies: Mieloproliferative disorders. Springer; 2007. p. 1-13.

  10. Goldman JM. Chronic myeloid leukemia: a historical perspective. Semin Hematol. 2010;47(4):302-11.

  11. Allan NC. Therapeutic options in chronic myeloid leukaemia. Blood Rev. 1989;3(1):45-52.

  12. Kantarjian HM, Smith TL, O’Brien S, et al. Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. Ann Intern Med. 1995;122:254-61.

  13. Gratwohl A, Hermans J, Goldman JM, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet. 1998;352:1087-92.

  14. Smith CC, Shah NP. Tyrosine kinase inhibitor therapy for chronic myeloid leukemia: Approach to patients with treatment-naive or refractory chronic- phase disease. Am Soc Hematol Educ Program. 2011;2011:121-7.

  15. Buchdunger E, Cioffi CL, Law N, et al. Abl protein kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-Kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther. 2000;295:139-45.

  16. Druker BJ, Talpaz M, Resta DJ, et al. Clinical efficacy and safety of an abl specific tyrosine kinase inhibitor as targeted therapy for chronic myeloid leukemia. N Engl J Med. 2001;344:1031-7.

  17. O’Brien SG, Guilhot F, Larson RA, 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.

  18. O’Brien SG, Guilhot F, Goldman JM, et al. International Randomized Study of Interferon and STI571 (IRIS) 7-year follow-up: sustained survival, low rate of transformation and increased rate of major molecular response in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib. Blood. 2008;112:76.

  19. Deininger M, O’Brien SG, Guilhot F, et al. 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 treated with imatinib. Blood. 2009;114(Suppl.):462.

  20. Mahon FX, Rea D, Guilhot J, et al. Intergroupe Français des Leucémies Myéloïdes Chroniques: 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;11:1029-35.

  21. Hochhaus A, La Rosée P. Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia. 2004;18:1321-31.

  22. Branford S, Rudzki Z, Walsh S, et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate- binding loop (P-loop) are associated with a poor prognosis. Blood. 2003;102: 276-83.

  23. Ernst T, Hoffmann J, Erben P, et al. ABL single nucleotide polymorphisms may masquerade as BCR-ABL mutations associated with resis tance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia. Haematologica. 2008;93:1389-93.

  24. Diamond J, Melo J. Mechanisms of resistance to BCR–ABL kinase inhibitors. Leukemia Lymphoma. 2011;52(S1):12-22.

  25. Coutre P, Tassi E, Varella-Garcia M, et al. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood. 2000;95:1758-66.

  26. Barnes D, Palaiologou D, Panousopoulou E, et al. Bcr-Abl expression levels determine the rate of development of resistance to imatinib mesylate in chronic myeloid leukemia. Cancer Res. 2005;65:8912-9.

  27. Leslie E, Deeley R, Cole S. Multidrug resistance proteins: role of P glycoprotein, MRP1, MRP2 and BCRP(ABCG2) in tissue defense. Toxicol App Pharm. 2005;204:216-37.

  28. Hamada A, Miyano H, Watanabe H, et al. Interaction of imatinib mesilate with human P-glycoprotein. J Pharm Exp Ther. 2003;307:824-8.

  29. Jordanides NE, Jorgensen HG, Holyoake TL, et al. Functional ABCG2 is over expressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood. 2006;108:1370-3.

  30. Thomas J, Wang L, Clark RE, et al. Active transport of imatinib into and out of cells: implications for drug resistance. Blood. 2004;104:3739-45.

  31. Engler J, Frede A, Saunders V, et al. Chronic Myeloid Leukemia CD34+ cells have reduced uptake of imatinib due to low OCT-1 activity. Leukemia. 2010;24:765-70.

  32. Holyoake TL, Jiang X, Jorgensen HG, et al. Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor-independent growth in vitro in association with up-regulation of expression of interleukin-3. Blood. 2001;97:720-8.

  33. Wang J, Lapidot T, Cashman J, et al. High level engraftment of NOD/ SCID mice by primitive normal and leukemic hematopoietic cells from patients with chronic myeloid leukemia in chronic phase. Blood. 1998;91:2406-14.

  34. Graham S, Jorgenssen H, Allan E, et al. Primitive quiescent Philadelphia positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood. 2002;99:319-25.

  35. Shah NP, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004;305:399-401.

  36. Wu J, Meng F, Kong LY, et al. Association between Imatinib-Resistant BCR-ABL Mutation-Negative Leukemia and Persistent Activation of LYN Kinase. J Natl Cancer Inst. 2008;100:926-39.

  37. Branford S, Hughes T, Nicoll J, et al. Molecular responses and mutation analysis in imatinib-resistant patients with Philadelphia Ph positive (Ph) leukemia with the dual Src/Abl kinase inhibitor BMS-354825. 10th Congress of the European Hematology Association. Estocolmo, Suecia, 2-5 de junio de 2005 [abstract].

  38. Baccarani M, Kantarjian HM, Apperley JF, et al. Efficacy of dasatinib (SPRYCEL) in patients (pts) with chronic phase chronic myelogenous leukemia (CP-CML) resistant to or intolerant of imatinib: updated results of the CA180013 START-C phase II study. Blood. 2006;108 [abstract 164].

  39. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260-70.

  40. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant bcr-abl. Cancer Cell. 2005;7:129-41.

  41. Saglio G, Kim DW, Issaragrisil S, et al. ENESTnd Investigators: Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251-9.

  42. Remsing Rix LL, Rix U, Colinge J, et al. Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009;23:477-85.

  43. Gambacorti-Passerini C, Cortes J, Khoury HJ, et al. Bosutinib (BOS) versus imatinib (IM) in patients with chronic phase chronic myeloid leukemia (CP CML) in the BELA trial: 18-month follow-up. American Society of Clinical Oncology Annual Meeting; 3-7 de junio de 2011; Chicago, IL [abstract 6509].

  44. O’Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16:401-12.

  45. Gozgit JM, Wong MJ, Wardwell S, et al. Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies. Mol Cancer Ther. 2011;10:1028-35.

  46. Cortes J, Talpaz M, Bixby D, et al. 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 (ASH Annual Meeting Abstracts). 2010;116.

  47. Aguayo A, Garcia-Alvarez E, Cazares-Ordonez Y, et al. Chronic Myeloid Leukemia: A Clinico epidemiologic and Therapeutic Description of a Single Institution in Mexico City. Clin Leuk. 2008;2:261-6.

  48. Hurtado-Monroy R, Vargas-Viveros P, Candelaria M, et al. Imatinib Compared with Imatinib/Cytarabine for the First-Line Treatment of Early Philadelphia Chromosome–Positive Chronic Myeloid Leukemia: Results of a Randomized Clinical Trial of the Mexican Collaborative Leukemia Group. Clin Leuk. 2008;2:128-32.

  49. Ayala M, Meillon L, Hurtado R, et al. Nilotinib AM107 can induce complete cytogenetic responses and molecular responses in patients with Chronic Myeloid Leukemia resistant or intolerant to imatinib mesylate. Report of the compassionate use program of Nilotinib in México. Haematologica. 2009;94 supp2:573.

  50. Kantarjian HM, Shah NP, Cortes JE, 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;119:1123-9.

  51. Ruiz-Arguelles GJ, Tarin-Arzaga LC, González-Carrillo ML, et al. Therapeutic choices in patients with Ph-positive CML living in Mexico in the tyrosine kinase inhibitor era: SCT or TKIs? Bone Marrow Transplant. 2008;42:23-8.

  52. Chávez-González A, Ayala-Sánchez M, Sánchez-Valle E, et al. Functional integrity in vitro of hematopoietic progenitor cells from patients with chronic myeloid leukemia that have achieved hematological remission after different therapeutic procedures. Leuk Res. 2006;30:286-95.

  53. Kinstrie R, Copland M. Targeting chronic myeloid leukemia stem cells. Curr Hematol Malig Rep. 2013;8:14-21.

  54. Chavez-Gonzalez A, Aviles-Vazquez S, Moreno-Lorenzana D, Mayani H. Hematopoietic Stem Cells in Chronic Myeloid Leukemia. En: Alimoghaddam K, ed. Stem Cell Biology in Normal Life and Disease. Intech; 2013. p. 137-64.

  55. Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013;121(22):4439-42.




2020     |     www.medigraphic.com