SpringerLink
Log in

The interferon-alpha revival in CML

  • Review Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Interferon-alpha (IFNα) was once the standard of frontline treatment for chronic myeloid leukemia (CML). Its pleiotropic mechanism of action in CML includes immune activation and specific targeting of CML stem cells. Early studies of IFNα in CML demonstrated that patients in chronic phase could attain extremely stable remissions, which correlated with long-term survival. Some patients even sustained their remission after discontinuing therapy, but the mechanism underlying this phenomenon is not well understood. Today, BCR-ABL tyrosine kinase inhibitors (TKIs), such as imatinib, induce remarkable responses in CML patients and have become the mainstay of CML therapy. Although TKIs target the pathogenic BCR-ABL protein in CML, they cannot fully eradicate CML stem cells. Some of the clinical trials testing IFNα plus imatinib combination therapy suggest that addition of IFNα increases the speed and rate of responses with imatinib therapy. However, the undesirable side effects of IFNα can make this therapy difficult to deliver, and the optimal therapeutic window for using IFNα in combination therapy is unknown. Further studies are needed to clarify the best niche for IFNα use in CML.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kotredes KP, Gamero AM (2013) Interferons as inducers of apoptosis in malignant cells. J Interf Cytokine Res : Off J Int Soc Interf Cytokine Res 33(4):162–170. doi:10.1089/jir.2012.0110

    Article  CAS  Google Scholar 

  2. Trinchieri G (2010) Type I interferon: friend or foe? J Exp Med 207(10):2053–2063. doi:10.1084/jem.20101664

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Platanias LC (2005) Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5(5):375–386. doi:10.1038/nri1604

    Article  CAS  PubMed  Google Scholar 

  4. Kiladjian JJ, Mesa RA, Hoffman R (2011) The renaissance of interferon therapy for the treatment of myeloid malignancies. Blood 117(18):4706–4715. doi:10.1182/blood-2010-08-258772

    Article  CAS  PubMed  Google Scholar 

  5. Fuchs SY (2013) Hope and fear for interferon: the receptor-centric outlook on the future of interferon therapy. J Interf Cytokine Res : Off J Int Soc Interf Cytokine Res 33(4):211–225. doi:10.1089/jir.2012.0117

    Article  CAS  Google Scholar 

  6. Der SD, Zhou A, Williams BR, Silverman RH (1998) Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays. Proc Natl Acad Sci U S A 95(26):15623–15628

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. de Veer MJ, Holko M, Frevel M, Walker E, Der S, Paranjape JM, Silverman RH, Williams BR (2001) Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol 69(6):912–920

    PubMed  Google Scholar 

  8. Chawla-Sarkar M, Lindner DJ, Liu YF, Williams BR, Sen GC, Silverman RH, Borden EC (2003) Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis. Apoptosis 8(3):237–249

    Article  CAS  PubMed  Google Scholar 

  9. Maher SG, Romero-Weaver AL, Scarzello AJ, Gamero AM (2007) Interferon: cellular executioner or white knight? Curr Med Chem 14(12):1279–1289

    Article  CAS  PubMed  Google Scholar 

  10. Bekisz J, Baron S, Balinsky C, Morrow A, Zoon KC (2010) Antiproliferative properties of type I and type II interferon. Pharmaceuticals 3(4):994–1015. doi:10.3390/ph3040994

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Stein BL, Tiu RV (2013) Biological rationale and clinical use of interferon in the classical BCR-ABL-negative myeloproliferative neoplasms. J Interf Cytokine Res : Off J Int Soc Interf Cytokine Res 33(4):145–153. doi:10.1089/jir.2012.0120

    Article  CAS  Google Scholar 

  12. Gutterman JU (1994) Cytokine therapeutics: lessons from interferon alpha. Proc Natl Acad Sci U S A 91(4):1198–1205

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. von Marschall Z, Scholz A, Cramer T, Schafer G, Schirner M, Oberg K, Wiedenmann B, Hocker M, Rosewicz S (2003) Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst 95(6):437–448

    Article  Google Scholar 

  14. Oliveira IC, Sciavolino PJ, Lee TH, Vilcek J (1992) Downregulation of interleukin 8 gene expression in human fibroblasts: unique mechanism of transcriptional inhibition by interferon. Proc Natl Acad Sci U S A 89(19):9049–9053

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Slaton JW, Perrotte P, Inoue K, Dinney CP, Fidler IJ (1999) Interferon-alpha-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin Cancer Res : Off J Am Assoc Cancer Res 5(10):2726–2734

    CAS  Google Scholar 

  16. Legros L, Guilhot J, Huault S, Mahon FX, Preudhomme C, Guilhot F, Hueber AO, French CMLG (2014) Interferon decreases VEGF levels in patients with chronic myeloid leukemia treated with imatinib. Leuk Res 38(6):662–665. doi:10.1016/j.leukres.2014.01.010

    Article  CAS  PubMed  Google Scholar 

  17. Indraccolo S (2010) Interferon-alpha as angiogenesis inhibitor: learning from tumor models. Autoimmunity 43(3):244–247. doi:10.3109/08916930903510963

    Article  CAS  PubMed  Google Scholar 

  18. Andrews DF 3rd, Singer JW, Coollins SJ (1987) Effect of recombinant α-interferon on the expression of the bcr-abl fusion gene in human chronic myelogenous human leukemia cell lines. Cancer Res 47(24 Pt 1):6629–6632

    CAS  PubMed  Google Scholar 

  19. Yanagisawa K, Yamauchi H, Kaneko M, Kohno H, Hasegawa H, Fujita S (1998) Suppression of cell proliferation and the expression of a bcr-abl fusion gene and apoptotic cell death in a new human chronic myelogenous leukemia cell line, KT-1, by interferon-α. Blood 91(2):641–648

    CAS  PubMed  Google Scholar 

  20. Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE, Davis MM (2000) Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 6(9):1018–1023

    Article  CAS  PubMed  Google Scholar 

  21. Tough DF, Borrow P, Sprent J (1996) Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272(5270):1947–1950

    Article  CAS  PubMed  Google Scholar 

  22. Hervas-Stubbs S, Riezu-Boj JI, Gonzalez I, Mancheno U, Dubrot J, Azpilicueta A, Gabari I, Palazon A, Aranguren A, Ruiz J, Prieto J, Larrea E, Melero I (2010) Effects of IFN-alpha as a signal-3 cytokine on human naive and antigen-experienced CD8(+) T cells. Eur J Immunol 40(12):3389–3402. doi:10.1002/eji.201040664

    Article  CAS  PubMed  Google Scholar 

  23. Lee CK, Rao DT, Gertner R, Gimeno R, Frey AB, Levy DE (2000) Distinct requirements for IFNs and STAT1 in NK cell function. J Immunol 165(7):3571–3577

    Article  CAS  PubMed  Google Scholar 

  24. Swann JB, Hayakawa Y, Zerafa N, Sheehan KC, Scott B, Schreiber RD, Hertzog P, Smyth MJ (2007) Type I IFN contributes to NK cell homeostasis, activation, and antitumor function. J Immunol 178(12):7540–7549

    Article  CAS  PubMed  Google Scholar 

  25. Rizza P, Moretti F, Belardelli F (2010) Recent advances on the immunomodulatory effects of IFN-alpha: implications for cancer immunotherapy and autoimmunity. Autoimmunity 43(3):204–209. doi:10.3109/08916930903510880

    Article  CAS  PubMed  Google Scholar 

  26. Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, Lee H, Arthur CD, White JM, Kalinke U, Murphy KM, Schreiber RD (2011) Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med 208(10):1989–2003. doi:10.1084/jem.20101158

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Giron-Michel J, Weill D, Bailly G, Legras S, Nardeux PC, Azzarone B, Tovey MG, Eid P (2002) Direct signal transduction via functional interferon-alphabeta receptors in CD34+ hematopoietic stem cells. Leukemia 16(6):1135–1142. doi:10.1038/sj.leu.2402492

    Article  CAS  PubMed  Google Scholar 

  28. Verma A, Deb DK, Sassano A, Uddin S, Varga J, Wickrema A, Platanias LC (2002) Activation of the p38 mitogen-activated protein kinase mediates the suppressive effects of type I interferons and transforming growth factor-beta on normal hematopoiesis. J Biol Chem 277(10):7726–7735. doi:10.1074/jbc.M106640200

    Article  CAS  PubMed  Google Scholar 

  29. Katsoulidis E, Carayol N, Woodard J, Konieczna I, Majchrzak-Kita B, Jordan A, Sassano A, Eklund EA, Fish EN, Platanias LC (2009) Role of Schlafen 2 (SLFN2) in the generation of interferon alpha-induced growth inhibitory responses. J Biol Chem 284(37):25051–25064. doi:10.1074/jbc.M109.030445

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Joshi S, Kaur S, Redig AJ, Goldsborough K, David K, Ueda T, Watanabe-Fukunaga R, Baker DP, Fish EN, Fukunaga R, Platanias LC (2009) Type I interferon (IFN)-dependent activation of Mnk1 and its role in the generation of growth inhibitory responses. Proc Natl Acad Sci U S A 106(29):12097–12102. doi:10.1073/pnas.0900562106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Aman MJ, Keller U, Derigs G, Mohamadzadeh M, Huber C, Peschel C (1994) Regulation of cytokine expression by interferon-alpha in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist. Blood 84(12):4142–4150

    CAS  PubMed  Google Scholar 

  32. Aman MJ, Bug G, Aulitzky WE, Huber C, Peschel C (1996) Inhibition of interleukin-11 by interferon-alpha in human bone marrow stromal cells. Exp Hematol 24(8):863–867

    CAS  PubMed  Google Scholar 

  33. Sato T, Onai N, Yoshihara H, Arai F, Suda T, Ohteki T (2009) Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion. Nat Med 15(6):696–700. doi:10.1038/nm.1973

    Article  CAS  PubMed  Google Scholar 

  34. Essers MA, Offner S, Blanco-Bose WE, Waibler Z, Kalinke U, Duchosal MA, Trumpp A (2009) IFNα activates dormant haematopoietic stem cells in vivo. Nature 458(7240):904–908. doi:10.1038/nature07815

    Article  CAS  PubMed  Google Scholar 

  35. Pietras EM, Lakshminarasimhan R, Techner JM, Fong S, Flach J, Binnewies M, Passegue E (2014) Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons. J Exp Med 211(2):245–262. doi:10.1084/jem.20131043

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Graham SM, Jørgensen HG, Allan E, Pearson C, Alcorn MJ, Richmond L, Holyoake TL (2002) Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 99(1):319–325

    Article  CAS  PubMed  Google Scholar 

  37. Copland M, Hamilton A, Elrick LJ, Baird JW, Allan EK, Jordanides N, Barow M, Mountford JC, Holyoake TL (2006) Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 107(11):4532–4539

    Article  CAS  PubMed  Google Scholar 

  38. Bhatia R, Holtz M, Niu N, Gray R, Snyder DS, Sawyers CL, Arber DA, Slovak ML, Forman SJ (2003) Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood 101(12):4701–4707

    Article  CAS  PubMed  Google Scholar 

  39. Mazur EM, Richtsmeier WJ, South K (1986) Alpha-interferon: differential suppression of colony growth from human erythroid, myeloid, and megakaryocytic hematopoietic progenitor cells. J Interferon Res 6(3):199–206

    Article  CAS  PubMed  Google Scholar 

  40. Ganser A, Carlo-Stella C, Greher J, Volkers B, Hoelzer D (1987) Effect of recombinant interferons alpha and gamma on human bone marrow-derived megakaryocytic progenitor cells. Blood 70(4):1173–1179

    CAS  PubMed  Google Scholar 

  41. Wang Q, Miyakawa Y, Fox N, Kaushansky K (2000) Interferon-alpha directly represses megakaryopoiesis by inhibiting thrombopoietin-induced signaling through induction of SOCS-1. Blood 96(6):2093–2099

    CAS  PubMed  Google Scholar 

  42. Yamane A, Nakamura T, Suzuki H, Ito M, Ohnishi Y, Ikeda Y, Miyakawa Y (2008) Interferon-alpha 2b-induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes. Blood 112(3):542–550. doi:10.1182/blood-2007-12-125906

    Article  CAS  PubMed  Google Scholar 

  43. Mayer IA, Verma A, Grumbach IM, Uddin S, Lekmine F, Ravandi F, Majchrzak B, Fujita S, Fish EN, Platanias LC (2001) The p38 MAPK pathway mediates the growth inhibitory effects of interferon-alpha in BCR-ABL-expressing cells. J Biol Chem 276(30):28570–28577

    Article  CAS  PubMed  Google Scholar 

  44. Lu M, Zhang W, Li Y, Berenzon D, Wang X, Wang J, Mascarenhas J, Xu M, Hoffman R (2010) Interferon-alpha targets JAK2V617F-positive hematopoietic progenitor cells and acts through the p38 MAPK pathway. Exp Hematol 38(6):472–480. doi:10.1016/j.exphem.2010.03.005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Hasan S, Lacout C, Marty C, Cuingnet M, Solary E, Vainchenker W, Villeval JL (2013) JAK2V617F expression in mice amplifies early hematopoietic cells and gives them a competitive advantage that is hampered by IFNalpha. Blood 122(8):1464–1477. doi:10.1182/blood-2013-04-498956

    Article  CAS  PubMed  Google Scholar 

  46. Selleri C, Sato T, Del Vecchio L, Luciano L, Barrett AJ, Rotoli B, Young NS, Maciejewski JP (1997) Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-α in chronic myelogenous leukemia. Blood 89(3):957–964

    CAS  PubMed  Google Scholar 

  47. Bhatia R, Verfaillie CM (1998) The effect of interferon-alpha on beta-1 integrin mediated adhesion and growth regulation in chronic myelogenous leukemia. Leuk Lymphoma 28(3–4):241–254

    CAS  PubMed  Google Scholar 

  48. Ito K, Tanaka H, Ito T, Sultana TA, Kyo T, Imanaka F, Ohmoto Y, Kimura A (2004) Initial expression of interferon alpha receptor 2 (IFNAR2) on CD34-positive cells and its down-regulation correlate with clinical response to interferon therapy in chronic myelogenous leukemia. Eur J Haematol 73(3):191–205. doi:10.1111/j.1600-0609.2004.00275.x

    Article  CAS  PubMed  Google Scholar 

  49. Biron CA (2001) Interferons alpha and beta as immune regulators—a new look. Immunity 14(6):661–664

    Article  CAS  PubMed  Google Scholar 

  50. Molldrem J, Dermime S, Parker K, Jiang YZ, Mavroudis D, Hensel N, Fukushima P, Barrett AJ (1996) Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood 88(7):2450–2457

    CAS  PubMed  Google Scholar 

  51. Burchert A, Muller MC, Kostrewa P, Erben P, Bostel T, Liebler S, Hehlmann R, Neubauer A, Hochhaus A (2010) Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia. J Clin Oncol : Off J Am Soc Clin Oncol 28(8):1429–1435. doi:10.1200/JCO.2009.25.5075

    Article  CAS  Google Scholar 

  52. Kanodia S, Wieder E, Lu S, Talpaz M, Alatrash G, Clise-Dwyer K, Molldrem JJ (2010) PR1-specific T cells are associated with unmaintained cytogenetic remission of chronic myelogenous leukemia after interferon withdrawal. PLoS One 5(7):e11770. doi:10.1371/journal.pone.0011770

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. Schepers K, Pietras EM, Reynaud D, Flach J, Binnewies M, Garg T, Wagers AJ, Hsiao EC, Passegue E (2013) Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche. Cell Stem Cell 13(3):285–299. doi:10.1016/j.stem.2013.06.009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Indraccolo S, Pfeffer U, Minuzzo S, Esposito G, Roni V, Mandruzzato S, Ferrari N, Anfosso L, Dell’Eva R, Noonan DM, Chieco-Bianchi L, Albini A, Amadori A (2007) Identification of genes selectively regulated by IFNs in endothelial cells. J Immunol 178(2):1122–1135

    Article  CAS  PubMed  Google Scholar 

  55. Takayanagi H, Kim S, Matsuo K, Suzuki H, Suzuki T, Sato K, Yokochi T, Oda H, Nakamura K, Ida N, Wagner EF, Taniguchi T (2002) RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Nature 416(6882):744–749. doi:10.1038/416744a

    Article  CAS  PubMed  Google Scholar 

  56. Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, Mizoguchi T, Wei Q, Lucas D, Ito K, Mar JC, Bergman A, Frenette PS (2013) Arteriolar niches maintain haematopoietic stem cell quiescence. Nature 502(7473):637–643. doi:10.1038/nature12612

    Article  CAS  PubMed  Google Scholar 

  57. Landolfo S, Guarini A, Riera L, Gariglio M, Gribaudo G, Cignetti A, Cordone I, Montefusco E, Mandelli F, Foa R (2000) Chronic myeloid leukemia cells resistant to interferon-alpha lack STAT1 expression. Hematol J : Off J Eur Haematol Assoc / EHA 1(1):7–14. doi:10.1038/sj/thj/6200004

    Article  CAS  Google Scholar 

  58. Pane F, Mostarda I, Selleri C, Salzano R, Raiola AM, Luciano L, Saglio G, Rotoli B, Salvatore F (1999) BCR/ABL mRNA and the P210(BCR/ABL) protein are downmodulated by interferon-alpha in chronic myeloid leukemia patients. Blood 94(7):2200–2207

    CAS  PubMed  Google Scholar 

  59. Schmidt M, Hochhaus A, Nitsche A, Hehlmann R, Neubauer A (2001) Expression of nuclear transcription factor interferon consensus sequence binding protein in chronic myeloid leukemia correlates with pretreatment risk features and cytogenetic response to interferon-alpha. Blood 97(11):3648–3650

    Article  CAS  PubMed  Google Scholar 

  60. Holtschke T, Lohler J, Kanno Y, Fehr T, Giese N, Rosenbauer F, Lou J, Knobeloch KP, Gabriele L, Waring JF, Bachmann MF, Zinkernagel RM, Morse HC 3rd, Ozato K, Horak I (1996) Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell 87(2):307–317

    Article  CAS  PubMed  Google Scholar 

  61. Hao SX, Ren R (2000) Expression of interferon consensus sequence binding protein (ICSBP) is downregulated in Bcr-Abl-induced murine chronic myelogenous leukemia-like disease, and forced coexpression of ICSBP inhibits Bcr-Abl-induced myeloproliferative disorder. Mol Cell Biol 20(4):1149–1161

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Schmidt M, Hochhaus A, Konig-Merediz SA, Brendel C, Proba J, Hoppe GJ, Wittig B, Ehninger G, Hehlmann R, Neubauer A (2000) Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy. J Clin Oncol : Off J Am Soc Clin Oncol 18(19):3331–3338

    CAS  Google Scholar 

  63. Mittrucker HW, Matsuyama T, Grossman A, Kundig TM, Potter J, Shahinian A, Wakeham A, Patterson B, Ohashi PS, Mak TW (1997) Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science 275(5299):540–543

    Article  CAS  PubMed  Google Scholar 

  64. Hochhaus A, Yan XH, Willer A, Hehlmann R, Gordon MY, Goldman JM, Melo JV (1997) Expression of interferon regulatory factor (IRF) genes and response to interferon-alpha in chronic myeloid leukaemia. Leukemia 11(7):933–939

    Article  CAS  PubMed  Google Scholar 

  65. Hasselbalch HC (2011) A new era for IFN-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Expert Rev Hematol 4(6):637–655. doi:10.1586/EHM.11.63

    Article  CAS  PubMed  Google Scholar 

  66. Simonsson B, Hjorth-Hansen H, Bjerrum OW, Porkka K (2011) Interferon alpha for treatment of chronic myeloid leukemia. Curr Drug Targets 12(3):420–428

    Article  CAS  PubMed  Google Scholar 

  67. Chronic Myeloid Leukemia Trialists’ Collaborative Group (1997) Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials. J Natl Cancer Inst 89(21):1616–1620

    Article  Google Scholar 

  68. Silver RT, Woolf SH, Hehlmann R, Appelbaum FR, Anderson J, Bennett C, Goldman JM, Guilhot F, Kantarjian HM, Lichtin AE, Talpaz M, Tura S (1999) 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 the American Society of Hematology. Blood 94(5):1517–1536

    CAS  PubMed  Google Scholar 

  69. Talpaz M, O’Brien S, Rose E, Gupta S, Shan J, Cortes J, Giles FJ, Faderl S, Kantarjian HM (2001) Phase 1 study of polyethylene glycol formulation of interferon α-2B (Schering 54031) in Philadelphia chromosome-positive chronic myelogenous leukemia. Blood 98(6):1708–1713

    Article  CAS  PubMed  Google Scholar 

  70. Lipton JH, Khoroshko N, Golenkov A, Abdulkadyrov K, Nair K, Raghunadharao D, Brummendorf T, Yoo K, Bergstrom B (2007) Phase II, randomized, multicenter, comparative study of peginterferon-α-2a (40 kD) (Pegasys®) versus interferon α-2a (Roferon®-A) in patients with treatment-naïve, chronic-phase chronic myelogenous leukemia. Leuk Lymphoma 48(3):497–505. doi:10.1080/10428190601175393

    Article  CAS  PubMed  Google Scholar 

  71. Michallet M, Maloisel F, Delain M, Hellmann A, Rosas A, Silver RT, Tendler C, Group PE-ICS (2004) Pegylated recombinant interferon alpha-2b vs recombinant interferon alpha-2b for the initial treatment of chronic-phase chronic myelogenous leukemia: a phase III study. Leukemia 18(2):309–315

    Article  CAS  PubMed  Google Scholar 

  72. Berenguer J, Gonzalez-Garcia J, Lopez-Aldeguer J, Von-Wichmann MA, Quereda C, Hernando A, Sanz J, Tural C, Ortega E, Mallolas J, Santos I, Miralles P, Montes ML, Bellon JM, Esteban H, Cohort GHH (2009) Pegylated interferon {alpha}2a plus ribavirin versus pegylated interferon {alpha}2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients. J Antimicrob Chemother 63(6):1256–1263. doi:10.1093/jac/dkp106

    Article  CAS  PubMed  Google Scholar 

  73. Laguno M, Cifuentes C, Murillas J, Veloso S, Larrousse M, Payeras A, Bonet L, Vidal F, Milinkovic A, Bassa A, Villalonga C, Perez I, Tural C, Martinez-Rebollar M, Calvo M, Blanco JL, Martinez E, Sanchez-Tapias JM, Gatell JM, Mallolas J (2009) Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients. Hepatology 49(1):22–31. doi:10.1002/hep.22598

    Article  CAS  PubMed  Google Scholar 

  74. Scotto G, Fazio V, Fornabaio C, Tartaglia A, Di Tullio R, Saracino A, Angarano G (2008) Early and sustained virological response in non-responders with chronic hepatitis C: a randomized open-label study of pegylated interferon-alpha-2a versus pegylated interferon-alpha-2b. Drugs 68(6):791–801

    Article  CAS  PubMed  Google Scholar 

  75. Kantarjian HM, O’Brien S, Cortes JE, Shan J, Giles FJ, Rios MB, Faderl SH, Wierda WG, Ferrajoli A, Verstovsek S, Keating MJ, Freireich EJ, Talpaz M (2003) Complete cytogenetic and molecular responses to interferon-alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer 97(4):1033–1041

    Article  CAS  PubMed  Google Scholar 

  76. Bonifazi F, de Vivo A, Rosti G, Guilhot F, Guilhot J, Trabacchi E, Hehlmann R, Hochhaus A, Shepherd PC, Steegmann JL, Kluin-Nelemans HC, Thaler J, Simonsson B, Louwagie A, Reiffers J, Mahon FX, Montefusco E, Alimena G, Hasford J, Richards S, Saglio G, Testoni N, Martinelli G, Tura S, Baccarani M (2001) Chronic myeloid leukemia and interferon-α: a study of complete cytogenetic responders. Blood 98(10):3074–3081

    Article  CAS  PubMed  Google Scholar 

  77. Malagola M, Breccia M, Skert C, Cancelli V, Soverini S, Iacobucci I, Cattina F, Liberati AM, Tiribelli M, Annunziata M, Trabacchi E, De Vivo A, Castagnetti F, Martinelli G, Fogli M, Stagno F, Pica G, Iurlo A, Pregno P, Abruzzese E, Pardini S, Bocchia M, Russo S, Pierri I, Lunghi M, Barulli S, Merante S, Mandelli F, Alimena G, Rosti G, Baccarani M, Russo D (2014) Long term outcome of Ph + CML patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era. Am J Hematol 89(2):119–124. doi:10.1002/ajh.23593

    Article  CAS  PubMed  Google Scholar 

  78. Mahon FX, Delbrel X, Cony-Makhoul P, Faberes C, Boiron JM, Barthe C, Bilhou-Nabera C, Pigneux A, Marit G, Reiffers J (2002) Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. J Clin Oncol : Off J Am Soc Clin Oncol 20(1):214–220

    Article  CAS  Google Scholar 

  79. Veneri D, Tecchio C, De Matteis G, Paviati E, Benati M, Franchini M, Pizzolo G (2012) Long-term persistence of molecular response after discontinuation of interferon-alpha in two patients with chronic myeloid leukaemia. Blood Transfus 10(2):233–234

    PubMed Central  PubMed  Google Scholar 

  80. Talpaz M, Estrov Z, Kantarjian H, Ku S, Foteh A, Kurzrock R (1994) Persistence of dormant leukemic progenitors during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies. J Clin Invest 94(4):1383–1389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Hochhaus A, Reiter A, Saussele S, Reichert A, Emig M, Kaeda J, Schultheis B, Berger U, Shepherd PC, Allan NC, Hehlmann R, Goldman JM, Cross NC (2000) Molecular heterogeneity in complete cytogenetic responders after interferon-α therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission. Blood 95(1):62–66

    CAS  PubMed  Google Scholar 

  82. Chomel JC, Brizard F, Veinstein A, Rivet J, Sadoun A, Kitzis A, Guilhot F, Brizard A (2000) Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-alpha therapy or allogeneic bone marrow transplantation. Blood 95(2):404–408

    CAS  PubMed  Google Scholar 

  83. Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P (2010) 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 11(11):1029–1035. doi:10.1016/S1470-2045(10)70233-3

    Article  CAS  PubMed  Google Scholar 

  84. Rowley JD (1973) Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243(5405):290–293

    Article  CAS  PubMed  Google Scholar 

  85. de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR (1982) A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature 300(5894):765–767

    Article  PubMed  Google Scholar 

  86. Shtivelman E, Lifshitz B, Gale RP, Canaani E (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315(6020):550–554

    Article  CAS  PubMed  Google Scholar 

  87. Daley GQ, Van Etten RA, Baltimore D (1990) Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 247(4944):824–830

    Article  CAS  PubMed  Google Scholar 

  88. Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J (1990) Acute leukaemia in bcr/abl transgenic mice. Nature 344(6263):251–253

    Article  CAS  PubMed  Google Scholar 

  89. O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ, Investigators I (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348(11):994–1004

    Article  PubMed  Google Scholar 

  90. Deininger M, O’Brien SG, Guilhot F, Goldman JM, Hochhaus A, Hughes TP, Radich JP, Hatfield AK, Mone M, Filian J, Reynolds J, Gathmann I, Larson RA, Druker BJ (2009) 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 114 (22):(abstract [1126])

  91. Hochhaus A, O’Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L, Goldman JM, Muller MC, Radich JP, Rudoltz M, Mone M, Gathmann I, Hughes TP, Larson RA, Investigators I (2009) Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 23(6):1054–1061. doi:10.1038/leu.2009.38

    Article  CAS  PubMed  Google Scholar 

  92. Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Muller MC, Pletsch N, Proetel U, Haferlach C, Schlegelberger B, Balleisen L, Hanel M, Pfirrmann M, Krause SW, Nerl C, Pralle H, Gratwohl A, Hossfeld DK, Hasford J, Hochhaus A, Saussele S (2011) 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 : Off J Am Soc Clin Oncol 29(12):1634–1642. doi:10.1200/JCO.2010.32.0598

    Article  CAS  Google Scholar 

  93. Hehlmann R, Muller MC, Lauseker M, Hanfstein B, Fabarius A, Schreiber A, Proetel U, Pletsch N, Pfirrmann M, Haferlach C, Schnittger S, Einsele H, Dengler J, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Ehninger G, Heim D, Heimpel H, Nerl C, Krause SW, Hossfeld DK, Kolb HJ, Hasford J, Saussele S, Hochhaus A (2014) Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. J Clin Oncol : Off J Am Soc Clin Oncol 32(5):415–423

    Article  CAS  Google Scholar 

  94. Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, Coiteux V, Gardembas M, Berthou C, Vekhoff A, Rea D, Jourdan E, Allard C, Delmer A, Rousselot P, Legros L, Berger M, Corm S, Etienne G, Roche-Lestienne C, Eclache V, Mahon FX, Guilhot F (2010) Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 363(26):2511–2521. doi:10.1056/NEJMoa1004095

    Article  CAS  PubMed  Google Scholar 

  95. Johnson-Ansah H, Guilhot J, Rousselot P, Rea D, Legros L, Rigal-Huguet F, Nicolini FE, Mahon FX, Preudhomme C, Guilhot F (2013) Tolerability and efficacy of pegylated interferon-alpha-2a in combination with imatinib for patients with chronic-phase chronic myeloid leukemia. Cancer 119(24):4284–4289. doi:10.1002/cncr.28328

    Article  CAS  PubMed  Google Scholar 

  96. Simonsson B, Gedde-Dahl T, Markevärn B, Remes K, Stentoft J, Almqvist A, Bjoreman M, Flogegard M, Koskenveesa P, Lindblom A, Malm C, Mustjoki S, Myhr-Eriksson K, Ohm L, Rasanen A, Sinisalo M, Sjalander A, Stromberg U, Weiss Bjerrum O, Ehrencrona H, Gruber F, Kairisto V, Olsson K, Sandin F, Nagler A, Lanng Nielsen J, Hjorth-Hansen H, Porkka K (2011) Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood 118:3228–3235. doi:10.1182/blood-2011-02-336685

    Article  CAS  PubMed  Google Scholar 

  97. Cortes J, Quintas-Cardama A, Jones D, Ravandi F, Garcia-Manero G, Verstovsek S, Koller C, Hiteshew J, Shan J, O’Brien S, Kantarjian H (2011) Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia: a randomized trial of frontline high-dose imatinib mesylate with or without pegylated interferon alpha-2b and granulocyte-macrophage colony-stimulating factor. Cancer 117(3):572–580. doi:10.1002/cncr.25438

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Palandri F, Iacobucci I, Castagnetti F, Testoni N, Poerio A, Amabile M, Breccia M, Intermesoli T, Iuliano F, Rege-Cambrin G, Tiribelli M, Miglino M, Pane F, Saglio G, Martinelli G, Rosti G, Baccarani M (2008) Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-α: 5-year outcome. Haematologica 93(5):770–774

    Article  CAS  PubMed  Google Scholar 

  99. Baccarani M, Martinelli G, Rosti G, Trabacchi E, Testoni N, Bassi S, Amabile M, Soverini S, Castagnetti F, Cilloni D, Izzo B, de Vivo A, Messa E, Bonifazi F, Poerio A, Luatti S, Giugliano E, Alberti D, Fincato G, Russo D, Pane F, Saglio G (2004) Imatinib and pegylated human recombinant interferon-α2b in early chronic-phase chronic myeloid leukemia. Blood 104(13):4245–4251

    Article  CAS  PubMed  Google Scholar 

  100. Palandri F, Castagnetti F, Iacobucci I, Martinelli G, Amabile M, Gugliotta G, Poerio A, Testoni N, Breccia M, Bocchia M, Crugnola M, Rege-Cambrin G, Martino B, Pierri I, Radaelli F, Specchia G, Pane F, Saglio G, Rosti G, Baccarani M (2010) The response to imatinib and interferon-α is more rapid than the response to imatinib alone: a retrospective analysis of 495 Philadelphia-positive chronic myeloid leukemia patients in early chronic phase. Haematologica 95(8):1415–1419

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Bedi A, Griffin CA, Barber JP, Vala MS, Hawkins AL, Sharkis SJ, Zehnbauer BA, Jones RJ (1994) Growth factor-mediated terminal differentiation of chronic myeloid leukemia. Cancer Res 54(21):5535–5538

    CAS  PubMed  Google Scholar 

  102. Angstreich GR, Matsui W, Huff CA, Vala MS, Barber J, Hawkins AL, Griffin CA, Smith BD, Jones RJ (2005) Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors. Br J Haematol 130(3):373–381

    Article  CAS  PubMed  Google Scholar 

  103. Paquette RL, Hsu N, Said J, Mohammed M, Rao NP, Shih G, Schiller G, Sawyers C, Glaspy JA (2002) Interferon-α induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo. Leukemia 16(8):1484–1489

    Article  CAS  PubMed  Google Scholar 

  104. Cortes J, Kantarjian H, O’Brien S, Kurzrock R, Keating M, Talpaz M (1998) GM-CSF can improve the cytogenetic response obtained with interferon-alpha therapy in patients with chronic myelogenous leukemia. Leukemia 12(6):860–864

    Article  CAS  PubMed  Google Scholar 

  105. Hardan I, Stanevsky A, Volchek Y, Tohami T, Amariglio N, Trakhtenbrot L, Koren-Michowitz M, Shimoni A, Nagler A (2012) Treatment with interferon alpha prior to discontinuation of imatinib in patients with chronic myeloid leukemia. Cytokine 57(2):290–293

    Article  CAS  PubMed  Google Scholar 

  106. Talpaz M, McCredie KB, Mavligit GM, Gutterman JU (1983) Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia. Blood 62(3):689–692

  107. Talpaz M, Kantarjian HM, McCredie KB, Keating MJ, Trujillo J, Gutterman J (1987) Clinical investigation of human alpha interferon in chronic myelogenous leukemia. Blood 69(5):1280–1288

  108. Alimena G, Morra E, Lazzarino M, Liberati AM, Montefusco E, Inverardi D, Bernasconi P, Mancini M, Donti E, Grignani F (1990) Interferon alpha-2b as therapy for patients with Ph'-positive chronic myelogenous leukemia. Eur J Haematol Suppl 52:25–28

  109. Talpaz M, Kantarjian H, Kurzrock R, Trujillo JM, Gutterman JU (1991) Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. Ann Intern Med 114(7):532–538

  110. Niederle N, Kloke O, Wandl UB, Becher R, Moritz T, Opalka B (1993) Long-term treatment of chronic myelogenous leukemia with different interferons: results from three studies. Leuk Lymphoma 9(1–2):111–119

  111. Ozer H, George SL, Schiffer CA, Rao K, Rao PN, Wurster-Hill DH, Arthur DD, Powell B, Gottlieb A, Peterson BA, Rai K, Testa JR, LeBeau M, Tantravahi R, Bloomfield CD (1993) Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583. Blood 82(10):2975–2984

  112. Thaler J, Gastl G, Fluckinger T, Niederwieser D, Huber H, Seewann H, Silly H, Lang A, Abbrederis C, Gadner H (1993) Treatment of chronic myelogenous leukemia with interferon alfa-2c: response rate and toxicity in a phase II multicenter study. Semin Hematol 30(3 Suppl 3):17–19

  113. Hehlmann R, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK, Queisser W, Loffler H, Hochhaus A, Heinze B (1994) Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. Blood 84(12):4064–4077

  114. Italian Cooperative Study Group on Chronic Myeloid Leukemia (1994) Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med 330(12):820–825

  115. Allan NC, Richards SM, Shepherd PC, on behalf of the UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia (1995) UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. Lancet 345(8962):1392–1397

  116. Ohnishi K, Ohno R, Tomonaga M, Kamada N, Onozawa K, Kuramoto A, Dohy H, Mizoguchi H, Miyawaki S, Tsubaki K (1995) A randomized trial comparing interferon-alpha with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase. Blood 86(3):906–916

  117. Kantarjian HM, Talpaz M, Keating MJ, Estey EH, O'Brien S, Beran M, McCredie KB, Gutterman J, Freireich EJ (1991) Intensive chemotherapy induction followed by interferon-alpha maintenance in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Cancer 68(6):1201–1207

  118. Kantarjian HM, Keating MJ, Estey EH, O'Brien S, Pierce S, Beran M, Koller C, Feldman E, Talpaz M (1992) Treatment of advanced stages of Philadelphia chromosome-positive chronic myelogenous leukemia with interferon-alpha and low-dose cytarabine. J Clin Oncol 10(5):772–778

  119. Hehlmann R, Berger U, Pfirrmann M, Hochhaus A, Metzgeroth G, Maywald O, Hasford J, Reiter A, Hossfeld DK, Kolb HJ, Loffler H, Pralle H, Queisser W, Griesshammer M, Nerl C, Kuse R, Tobler A, Eimermacher H, Tichelli A, Aul C, Wilhelm M, Fischer JT, Perker M, Scheid C, Schenk M, Weiss J, Meier CR, Kremers S, Labedzki L, Schmeiser T, Lohrmann HP, Heimpel H (2003) Randomized comparison of interferon a and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon a and hydroxyurea. Leukemia 17(8):1529–1537. doi:10.1038/sj.leu.24030062403006

  120. Kantarjian HM, O'Brien S, Smith TL, Rios MB, Cortes J, Beran M, Koller C, Giles FJ, Andreeff M, Kornblau S, Giralt S, Keating MJ, Talpaz M (1999) Treatment of Philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low-dose cytarabine. J Clin Oncol 17(1):284–292

  121. Arthur CK, Ma DD (1993) Combined interferon alfa-2a and cytosine arabinoside as first-line treatment for chronic myeloid leukemia. Acta Haematol 89:15–21

  122. Lindauer M, Domkin D, Döhner H, Kolb HJ, Neubauer A, Huhn D, Kreiter H, Koch B, Huber C, Aulitzky W, Fischer T (1999) Efficacy and toxicity of IFN-a2b combined with cytarabine in chronic myelogenous leukaemia. Br J Haematol 106(4):1013–1019

  123. Guilhot F, Chastang C, Michallet M, Guerci A, Harousseau JL, Maloisel F, Bouabdallah R, Guyotat D, Cheron N, Nicolini F, Abgrall JF, Tanzer J (1997) Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. N Engl J Med 337(4):223–229

  124. Baccarani M, Rosti G, de Vivo A, Bonifazi F, Russo D, Martinelli G, Testoni N, Amabile M, Fiacchini M, Montefusco E, Saglio G, Tura S, Italian Cooperative Study Group on Myeloid L (2002) A randomized study of interferon-a versus interferon-a and low-dose arabinosyl cytosine in chronic myeloid leukemia. Blood 99(5):1527–1535

Download references

Conflict of interest

MT has chaired a satellite symposium for Merck and has received drugs from Merck for clinical studies. The remaining authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, Comprehensive Cancer Center Room 4302, Ann Arbor, MI, 48109-5936, USA

    Moshe Talpaz & Jessica Mercer

  2. III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany

    Rüdiger Hehlmann

Authors
  1. Moshe Talpaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jessica Mercer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rüdiger Hehlmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moshe Talpaz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Talpaz, M., Mercer, J. & Hehlmann, R. The interferon-alpha revival in CML. Ann Hematol 94 (Suppl 2), 195–207 (2015). https://doi.org/10.1007/s00277-015-2326-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-015-2326-y

Keywords

Search

Navigation