Skip to main content

Advertisement

SpringerLink
Log in

The Cure of Chronic Myeloid Leukemia: Are We There Yet?

  • Leukemia (A Aguayo, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

A large number of chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKIs) can now enjoy a deep molecular control of the disease and the life span could be approaching that of normal population. The purpose of the review is to evaluate current evidence and if we can talk of a cure.

Recent Findings

The revolution in the treatment of CML was apparent since the exquisite efficacy of imatinib mesylate, a tyrosine kinase inhibitor, was proven and received approval for newly diagnosed cases in 2001. Subsequent development of second-generation TKIs, nilotinib and dasatinib, has increased our armamentarium. These TKIs, because of their safety and efficacy, are now offered as first-line therapy, thus relegating use of allogeneic transplant to the second line or beyond. It has also been possible to stop TKIs in selected subsets in whom leukemia burden became undetectable and ~ 40% of them remain drug-free for a number of years—treatment-free remission (TFR). Nevertheless, much work needs to be done to eradicate leukemia stem cells as current TKIs appear unable to eradicate leukemia stem cells (LSC). Effective treatment of more advanced phase CML remains elusive. Further efforts to develop newer molecules targeting BCR-ABL and beyond must be continued.

Summary

Although TKIs have revolutionized treatment of chronic phase CML, longer follow-up is necessary to realize their curative potential. Equally important is to explore newer targets and development of more potent small molecules for eradication of leukemia clone in all patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. Silver RT, Woolf SH, Hehlmann R, et al. An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for American Society of Hematology. Blood. 1999;94(1):1517–36.

    CAS  PubMed  Google Scholar 

  2. Thomas ED, Clift RA, Fefer A, Appelbaum FR, Beatty P, Bensinger WI, et al. Marrow transplantation for the treatment of chronic myelogenous leukemia. Ann Intern Med. 1986;104(2):155–63. https://doi.org/10.7326/0003-4819-104-2-155.

    Article  CAS  PubMed  Google Scholar 

  3. Talpaz M, McCredie KB, Mavligit GM, Gutterman JU. Leukocyte interferon induced myeloid cytoreduction in chronic myelogenous leukemia. Blood. 1983;62(3):689–92.

    CAS  PubMed  Google Scholar 

  4. Kantarjian HM, O’Brien S, Cortes JE, et al. Complete cytogenetic and molecular responses to interferon alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer. 2003;97(4):1033–41. https://doi.org/10.1002/cncr.11223.

    Article  CAS  PubMed  Google Scholar 

  5. Mahon FX, Debbrel X, Cony-Makhoul P, et al. Follow up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. J Clin Oncol. 2002;20(1):214–20. https://doi.org/10.1200/JCO.2002.20.1.214.

    Article  CAS  PubMed  Google Scholar 

  6. Huang X, Cortes J, Kantarjian H. Estimation of increasing prevalence and plateau of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Cancer. 2012;118(12):3123–7. https://doi.org/10.1002/cncr.26679.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bansal S, Kumar P, Parikh P. Chronic myeloid leukemia data from India. Ind J Med Ped Oncol. 2013;34(3):154–8. https://doi.org/10.4103/0971-5851.123711.

    Article  Google Scholar 

  8. Au WY, Caguioa PB, Chuah C, Hsu SC, Jootar S, Kim DW, et al. Chronic myeloid leukemia in Asia. Int J Hematol. 2009;89(1):14–23. https://doi.org/10.1007/s12185-008-0230-0.

    Article  PubMed  Google Scholar 

  9. Kumar L. Chronic myelogenous leukemia: an update. Nat Med J Ind. 2006;19:255–63.

    Google Scholar 

  10. • Delord M Jr. 100 years of chronic myeloid leukemia prevalence in France. Blood. 2016;128(22):2380. This study highlights the present and future burden of treating CML. The rising prevalence from 2/100,000 pre-imatinib era to 50/100,000 in coming decades will exponentially increase economic burden on individuals and society.

    Google Scholar 

  11. • Abboud C, Berman E, Cohen A, et al. 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. This article points out the unrealistic price of newer drugs used in cancer. This study stimulated further publications and debates on burden of cost of newly developed biological molecules.

    Article  PubMed Central  Google Scholar 

  12. Bower H, Bjorkholm M, Dickman PW, et al. Life expectancy of patients with chronic myeloid leukemia approaches of the life expectancy of the general population. J Clin Oncol. 2016;34(24):2851–7. https://doi.org/10.1200/JCO.2015.66.2866.

    Article  CAS  PubMed  Google Scholar 

  13. Fialkow PJ, Jacobson RJ, Papayanapoulou T. Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelets and monocyte/macrophage. Am J Med. 1977;63(1):125–30. https://doi.org/10.1016/0002-9343(77)90124-3.

    Article  CAS  PubMed  Google Scholar 

  14. Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst. 1960;25(1):85–109.

    CAS  PubMed  Google Scholar 

  15. Rowley J. A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine and Giemsa staining. Nature. 1973;243(5405):290–3. https://doi.org/10.1038/243290a0.

    Article  CAS  PubMed  Google Scholar 

  16. Heistercamp N, Storm K, Groffen J, de Klein A, Grosveld G. Structural organization of the bcr gene and its role in the Ph’ translocation. Nature. 1985;315(6022):758–61. https://doi.org/10.1038/315758a0.

    Article  Google Scholar 

  17. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by p210/bcr/abl gene of Philadelphia chromosome. Science. 1990;247(4944):824–30. https://doi.org/10.1126/science.2406902.

    Article  CAS  PubMed  Google Scholar 

  18. Holyoake T, Jiang X, Eaves C, Eaves A. Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood. 1999;94(6):2056–64.

    CAS  PubMed  Google Scholar 

  19. Barnes DJ, Melo JV. Primitive, quiescent and difficult to kill: the role of non-proliferating cells in chronic myeloid leukemia. Cell Cycle. 2006;5(24):2862–6. https://doi.org/10.4161/cc.5.24.3573.

    Article  CAS  PubMed  Google Scholar 

  20. Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cell in blast crisis CML. N Engl J Med. 2004;351(7):657–67. https://doi.org/10.1056/NEJMoa040258.

    Article  CAS  PubMed  Google Scholar 

  21. Jamieson CH, Weissman IL, Passegue’ E. Chronic versus acute myelogenous leukemia: a question of self-renewal. Cancer Cell. 2004;6(6):531–3. https://doi.org/10.1016/j.ccr.2004.12.005.

    CAS  PubMed  Google Scholar 

  22. •• Holyoake T, Vetrie D. The chronic myeloid leukemia stem cell: stemming the tide of persistence. Blood. 2017;129(12):1595–606. This extensive review on CML stem cells, discusses persistence of LSC despite very effective TKIs and the challenge in curing CML. There are biological pathways that escape TKIs and are responsible for resistance, relapse and progression of disease phase. https://doi.org/10.1182/blood-2016-09-696013.

    Article  CAS  PubMed  Google Scholar 

  23. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;555:1990.

    Google Scholar 

  24. Kolb HJ, Mittermuller J, Clemm C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 76:2462–5.

  25. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998;91(3):756–63.

    CAS  PubMed  Google Scholar 

  26. Or R, Shapira MA, Resnick I, et al. Nonmyeloablative allogeneic stem cell transplantation for treatment of chronic myeloid leukemia in first chronic phase. Blood. 2003;101(2):441–5. https://doi.org/10.1182/blood-2002-02-0535.

    Article  CAS  PubMed  Google Scholar 

  27. Das M, Saikia TK, Advani SH, Parikh PM, Tawde S. Use of reduced-intensity conditioning for allogeneic transplantation in patients with chronic myeloid leukemia. Bone Marrow Transplant. 2003;32:125–9.

  28. Crawley C, Szyldo R, Lalancette M, et al. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT. Blood. 2005;106(9):2969–76. https://doi.org/10.1182/blood-2004-09-3544.

    Article  CAS  PubMed  Google Scholar 

  29. Bittencourt H, Funke V, Fogliatto L, Magalhães S, Setubal D, Paz A, et al. Imatinib mesylate versus allogeneic BMT for patients with chronic myeloid leukemia in first chronic phase. Bone Marrow Transplant. 2008;42(9):597–600. https://doi.org/10.1038/bmt.2008.218.

    Article  CAS  PubMed  Google Scholar 

  30. Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, et al. Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood. 2007;109(11):4686–92. https://doi.org/10.1182/blood-2006-11-055186.

    Article  CAS  PubMed  Google Scholar 

  31. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Blood. 2013;122(6):6041–6051.

  32. Talpaz M, Kantarjian H, Kurzrock R, Guttermann JU. Interferon alpha in the therapy of CML. Br J Haematol. 1991;79(s1):38–41. https://doi.org/10.1111/j.1365-2141.1991.tb08117.x.

    Article  PubMed  Google Scholar 

  33. Guilhot F, Chastang C, Michallet M, Guerci A, Harousseau JL, Maloisel F, et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. N Engl J Med. 1997;337(4):223–9. https://doi.org/10.1056/NEJM199707243370402.

    Article  CAS  PubMed  Google Scholar 

  34. O’Brien SG, Guilhot F, Larson R, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348(11):994–1004. https://doi.org/10.1056/NEJMoa022457.

    Article  PubMed  Google Scholar 

  35. Preudhomme C, Guilhot J, Nicolini FE, et al. Imatinib plus peg-interferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010;3639:2511–21.

    Article  Google Scholar 

  36. Polivkova V, Rohon P, Klamova H, Cerna O, Divoka M, Curik N, et al. Interferon-α revisited: individualized treatment management eased the selective pressure of tyrosine kinase inhibitors on BCR-ABL1 mutations resulting in a molecular response in high-risk CML patients. PLoS One. 2016;11(5):e0155959. https://doi.org/10.1371/journal.pone.0155959.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Buchdunger E, Zimmermann J, Mett H, Meyer T, Müller M, Druker BJ, et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 1996;56(1):100–4.

    CAS  PubMed  Google Scholar 

  38. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, et al. Effects of selective inhibitor of Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2(5):561–6. https://doi.org/10.1038/nm0596-561.

    Article  CAS  PubMed  Google Scholar 

  39. Deininger M, Buchdunger E, Druker BJ. The development of imatinib as therapeutic agent for chronic myeloid leukemia. Blood. 2005;105(7):2640–53. https://doi.org/10.1182/blood-2004-08-3097.

    Article  CAS  PubMed  Google Scholar 

  40. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, 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):1031–7. https://doi.org/10.1056/NEJM200104053441401.

    Article  CAS  PubMed  Google Scholar 

  41. 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(23):2408–17. https://doi.org/10.1056/NEJMoa062867.

    Article  CAS  PubMed  Google Scholar 

  42. Hochhaus A. O’Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23(6):1054–1061.

  43. Hochhaus A, Larson R, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917–27. https://doi.org/10.1056/NEJMoa1609324.

    Article  CAS  PubMed  Google Scholar 

  44. Saglio G, Kim D-W, Issaragrisiil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251–9. https://doi.org/10.1056/NEJMoa0912614.

    Article  CAS  PubMed  Google Scholar 

  45. •• Hochhaus A, Sagloi G, Hughes TP, et al. Long-term benefit and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. N Engl J Med. 2016;30:1044–54. This latest analysis of long-term survival of CML-CP receiving imatinib proves the utility, with more than 80% long-term survival at 10-year median follow-up.

    CAS  Google Scholar 

  46. 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(24):2260–70. https://doi.org/10.1056/NEJMoa1002315.

    Article  CAS  PubMed  Google Scholar 

  47. Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqué C, et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34(20):2333–40. https://doi.org/10.1200/JCO.2015.64.8899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Soverini S, Rosti G, Iacobucci I, Baccarani M, Martinelli G. Choosing the best second-line tyrosine kinase inhibitor in imatinib-resistant chronic myeloid leukemia patients harboring Bcr-Abl kinase domain mutations: how reliable is the IC50? Oncologist. 2011;16(6):868–76. https://doi.org/10.1634/theoncologist.2010-0388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicius L, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol. 2012;30(28):3486–92. https://doi.org/10.1200/JCO.2011.38.7522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lipton JH, Chuah C, Guerci-Bresier A, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukemia: an international, randomized, open label, phase 3 trial. Lancet Oncol. 2016;17(5):612–21. https://doi.org/10.1016/S1470-2045(16)00080-2.

    Article  CAS  PubMed  Google Scholar 

  51. Cortes JE, Pinilla-Ibarz J, Le Coutre PD, et al. 4-year results of the ponatinib phase II PACE trial in patients (pts) with heavily pretreated leukemia. J Clin Oncol. 2016(suppl), abstr, 7013.

  52. Mahon FX, Guilhot RD, Guilhot 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, multicenter Stop Imatinib (STM) trial. Lancet Oncol. 2010;11(11):1029–35. https://doi.org/10.1016/S1470-2045(10)70233-3.

    Article  CAS  PubMed  Google Scholar 

  53. •• Etienne G, Guilhot J, Rea D, Rigal-Huguet F, Nicolini F, Charbonnier A, et al. Long-term follow-up of the French Stop Imatinib (STM1) study in patients with chronic myeloid leukemia. J Clin Oncol. 2016;35(3):298–305. https://doi.org/10.1200/JCO.2016.68.2914. This study is 77-month median follow-up of 100 patients who stopped imatinib. The median molecular leukemia recurrence-free survival (MRFS) was 43% at 6 months and 38% at 60 months. Restarting treatment could bring about second undetectable MRD in 55 of 61 patients within a median of 4 months.

    Article  PubMed  Google Scholar 

  54. Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122(4):525–2.

    Article  Google Scholar 

  55. •• Mahon FX. Cessation of tyrosine kinase inhibitors treatment in chronic myeloid leukemia patients with deep molecular response: results of the Euro-Ski trial. Blood. 2016;128:787. This largest study of stop TKI presented in December ASH 2016 Meeting included 750 patients (out of 821 included) on imatinib, nilotinib, and dasatinib had molecular data for estimation of MRFS. Three hundred forty-eight lost MMR; MRFS was 62% at 6 months, 56% at 12 months, and 52% at 24 months. Inclusion criteria needed deep molecular (DMR, BCR-ABL level 0.01% on International Scale) for the duration of at least 1 year; molecular relapse was defined by the loss of major molecular response (MMR, BCR-ABL level < 0.1% IS) at any one point. Longer imatinib therapy (optimal–5.8 years) prior to TKI-stop was associated with higher probability of MRFS.

  56. •• Rousselot P, Charbonnier A, Cony-Makhoul P, Agape P, Nicolini FE, Varet B, et al. Loss of major molecular response as a trigger for restarting tyrosine inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol;2014;32(5):424–30. https://doi.org/10.1200/JCO.2012.48.5797. This study included 80 patients on imatinib who were on prolonged imatinib therapy (median 79 months, range 30–145 months) and median CMR of 41 months (24–96 months). The deviation from the earlier studies (STIM and TWISTER) was resumption of a TKI after loss of major molecular response (MMR), rather than any increase in BCR-ABL level. With a median follow-up of 31 months (8–92 months) discontinuation of imatinib, 29 (36%) patients lost MMR after a median of 4 months (2–17 months) and cumulative loss of MR was 35% at 12 months and 36% at 24 months., whereas losing CMR was higher. Treatment-free remission (TFR) was estimated as 64% at 12 and 24 months and 61% at 36 months. The median time to second CMR estimated as 7.3 months on re-treatment.

  57. Clarke RE, Polydoros F, Apperley KF et al. Chronic myeloid leukemia patients with stable molecular responses (at least DMR) may safely decrease the dose of their tyrosine kinase inhibitor: Data from the British Destiny Study. 2016. ASH Annual Meeting. Abstract 938.

  58. Hughes A, Yong ASM. Immune effector recovery in chronic myeloid leukemia and treatment-free remission. Front Immunol. 2017;8 https://doi.org/10.3389/fimmu.2017.00469.

  59. Melo JV, Ross DM. Minimal residual disease and discontinuation of therapy in chronic myeloid leukemia: can we aim at a cure? Hematology Am Soc Hematol Program. 2011;2011:136–42.

    Google Scholar 

  60. 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;106:28–37.

    Article  Google Scholar 

  61. •• Cross NCP, White HE, Colomer D, Ehrencrona H, Foroni L, Gottardi E, et al. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia. Leukemia. 2015;29(5):999–1003. https://doi.org/10.1038/leu.2015.29. This important study describes the methodology for accurate definition of deep molecular responses for optimal management and comparison of independent data sets, developed as a part of the European Treatment and Outcome Study for CML (EUTOS).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Michor F, Hughes TP, Iwasa Y, Branford S, Shah NP, Sawyers CL, et al. Dynamics of chronic myeloid leukemia. Nature. 2005;435(7046):1267–70. https://doi.org/10.1038/nature03669.

    Article  CAS  PubMed  Google Scholar 

  63. Tang M, Gonen M, Quintas-Cardama A, Cortes J, Kantarjian H, Field C, et al. Dynamics of chronic myeloid leukemia response to long-term targeted therapy reveal treatment effects on leukemia stem cells. Blood. 2011;118(6):1622–31. https://doi.org/10.1182/blood-2011-02-339267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Roeder I, Glauche HM, Hochhaus A, et al. Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implications. Nat Med. 2002;12(10):1181–4.

    Article  Google Scholar 

  65. Lenaerts T, Pacheo JM, Traulsen A, Dingly D. Tyrosine kinase inhibitor therapy can cure chronic myeloid leukemia without hitting leukemic stem cells. Haematologica. 2010;95(6):900–7. https://doi.org/10.3324/haematol.2009.015271.

    Article  CAS  PubMed  Google Scholar 

  66. Bhatia R, Holtz M, Niu N, et al. Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia in complete cytogenetic remission following imatinib mesylate treatment. Blood. 2003;118(20):4701–7.

    Article  Google Scholar 

  67. Chomel JC, Bonnet ML, Sorel N, Bertrand A, Meunier MC, Fichelson S, et al. Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual disease. Blood. 2011;118(13):3657–60. https://doi.org/10.1182/blood-2011-02-335497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hamilton A, Helgason GV, Scheminek M, et al. Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival. Blood. 2012;119(6):1501–10. https://doi.org/10.1182/blood-2010-12-326843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Carter BZ, Andreeff M. Eradication of CML stem cells. Oncoscience. 2016;3(11–12):313–5. https://doi.org/10.18632/oncoscience.327.

    PubMed  PubMed Central  Google Scholar 

  70. Zhou H, Mak PY, Mu H, Mak DH, Zeng Z, Cortes J, et al. Combined inhibition of β-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo. Leukemia. 2017;31(10):2065–74. https://doi.org/10.1038/leu.2017.87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Longo D. Imatinib changed everything. N Engl J Med. 2017;376(10):982–3. https://doi.org/10.1056/NEJMe1700833.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Prince Aly Khan Hospital, Mumbai, 400010, India

    Tapan Saikia

Authors
  1. Tapan Saikia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tapan Saikia.

Ethics declarations

Conflict of Interest

Tapan Saikia declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Leukemia

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saikia, T. The Cure of Chronic Myeloid Leukemia: Are We There Yet?. Curr Oncol Rep 20, 12 (2018). https://doi.org/10.1007/s11912-018-0665-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-018-0665-2

Keywords

Search

Navigation