Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

References

• Kantarjian H, O’Brien S, Jabbour E, et al. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood 2012;119:1981–1987.
   PubMed Web of Science ®Google Scholar
• Bjorkholm M, Ohm L, Eloranta S, et al. Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008. J Clin Oncol 2011;29:2514–2520.
   PubMed Web of Science ®Google Scholar
• Hehlmann R. How I treat CML blast crisis. Blood 2012;120: 737–747.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Keating MJ, Smith TL, et al. Proposal for a simple synthesis prognostic staging system in chronic myelogenous leukemia. Am J Med 1990;88:1–8.
   PubMed Web of Science ®Google Scholar
• Savage DG, Szydlo RM, Chase A, et al. Bone marrow transplantation for chronic myeloid leukaemia: the effects of differing criteria for defining chronic phase on probabilities of survival and relapse. Br J Haematol 1997;99:30–35.
   PubMed Web of Science ®Google Scholar
• Sokal JE, Baccarani M, Russo D, et al. Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 1988;25:49–61.
   PubMed Web of Science ®Google Scholar
• Swerdlow SH, Campo E, Harris NL, et al., editors. World Health Organization classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Geneva: WHO Press; 2008.
   Google Scholar
• Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809–1820.
   PubMed Web of Science ®Google Scholar
• Cortes JE, Talpaz M, O’Brien S, et al. Staging of chronic myeloid leukemia in the imatinib era. Cancer 2006;106:1306–1315.
   PubMed Web of Science ®Google Scholar
• Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960;25:85–109.
   PubMed Web of Science ®Google Scholar
• Shtivelman E, Lifshitz B, Gale RP, et al. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 1985;315:550–554.
   PubMed Web of Science ®Google Scholar
• Perrotti D, Jamieson C, Goldman J, et al. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest 2010;120:2254–2264.
   PubMed Web of Science ®Google Scholar
• Gaiger A, Henn T, Horth E, et al. Increase of bcr-abl chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression. Blood 1995;86:2371–2378.
   PubMed Web of Science ®Google Scholar
• Lin F, van Rhee F, Goldman JM, et al. Kinetics of increasing BCR-ABL transcript numbers in chronic myeloid leukemia patients who relapse after bone marrow transplantation. Blood 1996;87:4473–4478.
   PubMed Web of Science ®Google Scholar
• Lahaye T, Riehm B, Berger U, et al. Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer 2005;103:1659–1669.
   PubMed Web of Science ®Google Scholar
• Koptyra M, Falinski R, Nowicki MO, et al. BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance. Blood 2006;108:319–327.
   PubMed Web of Science ®Google Scholar
• Sattler M, Verma S, Shrikhande G, et al. The BCR/ABL tyrosine kinase induces production of reactive oxygen species in hematopoietic cells. J Biol Chem 2000;275:24273–24278.
   PubMed Web of Science ®Google Scholar
• Flis K, Irvine D, Copland M, et al. Chronic myeloid leukemia stem cells display alterations in expression of genes involved in oxidative phosphorylation. Leuk Lymphoma 2012;53:2474–2478.
   PubMed Web of Science ®Google Scholar
• Nowicki MO, Falinski R, Koptyra M, et al. BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks. Blood 2004;104:3746–3753.
   PubMed Web of Science ®Google Scholar
• Deutsch E, Dugray A, Abdul Karim B, et al. BCR-ABL down-regulates the DNA repair protein DNA-PKcs. Blood 2001;97:2084–2090.
   PubMed Web of Science ®Google Scholar
• Slupianek A, Hoser G, Majsterek I, et al. Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis. Mol Cell Biol 2002;22:4189–4201.
   PubMed Web of Science ®Google Scholar
• Slupianek A, Poplawski T, Jozwiakowski SK, et al. BCR/ABL stimulates WRN to promote survival and genomic instability. Cancer Res 2011;71:842–851.
   PubMed Web of Science ®Google Scholar
• Slupianek A, Dasgupta Y, Ren SY, et al. Targeting RAD51 phosphotyrosine-315 to prevent unfaithful recombination repair in BCR-ABL1 leukemia. Blood 2011;118:1062–1068.
   PubMed Web of Science ®Google Scholar
• Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol 2002;107:76–94.
   PubMed Web of Science ®Google Scholar
• Mitelman F, Levan G, Nilsson PG, et al. Non-random karyotypic evolution in chronic myeloid leukemia. Int J Cancer 1976;18:24–30.
   PubMed Web of Science ®Google Scholar
• Jennings BA, Mills KI. c-myc locus amplification and the acquisition of trisomy 8 in the evolution of chronic myeloid leukaemia. Leuk Res 1998;22:899–903.
   PubMed Web of Science ®Google Scholar
• Honda H, Ushijima T, Wakazono K, et al. Acquired loss of p53 induces blastic transformation in p210(bcr/abl)-expressing hematopoietic cells: a transgenic study for blast crisis of human CML. Blood 2000;95:1144–1150.
   PubMed Web of Science ®Google Scholar
• Iervolino A, Santilli G, Trotta R, et al. hnRNP A1 nucleocytoplasmic shuttling activity is required for normal myelopoiesis and BCR/ABL leukemogenesis. Mol Cell Biol 2002;22:2255–2266.
   PubMed Web of Science ®Google Scholar
• von Lindern M, van Baal S, Wiegant J, et al. Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3’ half to different genes: characterization of the set gene. Mol Cell Biol 1992;12:3346–3355.
   PubMed Web of Science ®Google Scholar
• Neviani P, Santhanam R, Trotta R, et al. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell 2005;8:355–368.
   PubMed Web of Science ®Google Scholar
• Li M, Makkinje A, Damuni Z. The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A. J Biol Chem 1996;271:11059–11062.
   PubMed Web of Science ®Google Scholar
• Perrotti D, Neviani P. ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia. Br J Cancer 2006;95:775–781.
   Google Scholar
• Eiring AM, Neviani P, Santhanam R, et al. Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood 2008;111:816–828.
   Google Scholar
• Bornens M. The centrosome in cells and organisms. Science 2012;335:422–426.
   PubMed Web of Science ®Google Scholar
• Chan JY. A clinical overview of centrosome amplification in human cancers. Int J Biol Sci 2011;7:1122–1144.
   PubMed Web of Science ®Google Scholar
• Giehl M, Fabarius A, Frank O, et al. Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability. Leukemia 2005;19:1192–1197.
   PubMed Web of Science ®Google Scholar
• Patel H, Gordon MY. Abnormal centrosome-centriole cycle in chronic myeloid leukaemia?Br J Haematol 2009;146:408–417.
   PubMed Web of Science ®Google Scholar
• Giehl M, Leitner A, Haferlach C, et al. Detection of centrosome aberrations in disease-unrelated cells from patients with tumor treated with tyrosine kinase inhibitors. Eur J Haematol 2010;85:139–148.
   PubMed Web of Science ®Google Scholar
• Stein BL. Chronic myeloid leukemia and risk of second malignancy in two eras of treatment. Leuk Lymphoma 2012;53:1651–1653.
   PubMed Web of Science ®Google Scholar
• Blackburn EH. Structure and function of telomeres. Nature 1991;350:569–573.
   PubMed Web of Science ®Google Scholar
• Raynaud CM, Sabatier L, Philipot O, et al. Telomere length, telomeric proteins and genomic instability during the multistep carcinogenic process. Crit Rev Oncol Hematol 2008;66:99–117.
   PubMed Web of Science ®Google Scholar
• Brümmendorf TH, Holyoake TL, Rufer N, et al. Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry. Blood 2000;95:1883–1890.
   PubMed Web of Science ®Google Scholar
• Drummond M, Lennard A, Brummendorf T, et al. Telomere shortening correlates with prognostic score at diagnosis and proceeds rapidly during progression of chronic myeloid leukemia. Leuk Lymphoma 2004;45:1775–1781.
   PubMed Web of Science ®Google Scholar
• Wong KK, Chang S, Weiler SR, et al. Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat Genet 2000;26:85–88.
   PubMed Web of Science ®Google Scholar
• Plentz RR, Schlegelberger B, Flemming P, et al. Telomere shortening correlates with increasing aneuploidy of chromosome 8 in human hepatocellular carcinoma. Hepatology 2005;42:522–526.
   PubMed Web of Science ®Google Scholar
• Brümmendorf TH, Ersoz I, Hartmann U, et al. Normalization of previously shortened telomere length under treatment with imatinib argues against a preexisting telomere length deficit in normal hematopoietic stem cells from patients with chronic myeloid leukemia. Ann NY Acad Sci 2003;996:26–38.
   PubMed Web of Science ®Google Scholar
• Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA 2006;103:2794–2799.
   PubMed Web of Science ®Google Scholar
• Nowicki MO, Pawlowski P, Fischer T, et al. Chronic myelogenous leukemia molecular signature. Oncogene 2003;22:3952–3963.
   PubMed Web of Science ®Google Scholar
• Zheng C, Li L, Haak M, et al. Gene expression profiling of CD34 + cells identifies a molecular signature of chronic myeloid leukemia blast crisis. Leukemia 2006;20:1028–1034.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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 (CML-CP) treated with imatinib. Blood 2009;114(Suppl. 1): Abstract 1126.
   Google Scholar
• Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006;355:2408–2417.
   PubMed Web of Science ®Google Scholar
• 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;23:1054–1061.
   PubMed Web of Science ®Google Scholar
• Hehlmann R, Lauseker M, Jung-Munkwitz S, 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.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Hochhaus A, Saglio G, 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.
   PubMed Web of Science ®Google Scholar
• Larson RA, Hochhaus A, Hughes TP, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 2012;26:2197–2203.
   PubMed Web of Science ®Google Scholar
• Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251–2259.
   PubMed Web of Science ®Google Scholar
• Cortes JE, Jones D, O’Brien S, et al. Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol 2010;28:392–397.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Kantarjian HM, Luthra R, et al. Efficacy of frontline nilotinib therapy in patients (Pts) with newly diagnosed Philadelphia chromosome (Ph)-positive chronic myeloid leukemia in early chronic phase (CML-CP). Blood 2011;118(Suppl. 1): Abstract 454.
   Google Scholar
• Gugliotta G, Castagnetti F, Breccia M, et al. Early CP CML, nilotinib 400 mg twice daily frontline: beyond 3 years, results remain excellent and stable (a GIMEMA CML Working Party Trial). Blood 2011;118(Suppl. 1): Abstract 2756.
   Google Scholar
• Rosti G, Palandri F, Castagnetti F, et al. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood 2009;114: 4933–4938.
   PubMed Web of Science ®Google Scholar
• O’Dwyer EO, Swords R, Giles F, et al. Nilotinb 300 mg twice daily is effective and well tolerated as first line treatment of Ph-positive chronic myeloid leukemia in chronic phase: updated results of the ICORG 0802 phase study. Haematologica 2010;95(Suppl.):340, Abstract 0812.
   PubMed Web of Science ®Google Scholar
• O’Dwyer MC, Kent E, Parker M, et al. Nilotinib 300 mg twice daily is effective and well tolerated as first line treatment of Ph-positive chronic myeloid leukemia in chronic phase: preliminary results of the ICORG 0802 phase 2 study. Blood 2009;114(Suppl. 1): Abstract 3294.
   Google Scholar
• O’Dwyer ME, Swords R, Giles F, et al. Analysis of the GeneXpert System on the international multicentre ICORG 08-02 phase II study of nilotinib 300mg BID as frontline treatment in patients with early chronic phase chronic myeloid leukemia (ECPCML). Blood 2011;118(Suppl. 1): Abstract 3774.
   Google Scholar
• Hochhaus A, Shah NP, Cortes JE, et al. Dasatinib versus imatinib (IM) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): DASISION 3-year follow-up. J Clin Oncol 2012;30(Suppl.): Abstract 6504.
   Google Scholar
• Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260–2270.
   PubMed Web of Science ®Google Scholar
• 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;119:1123–1129.
   PubMed Web of Science ®Google Scholar
• Cortes JE, Jones D, O’Brien S, et al. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol 2010;28:398–404.
   PubMed Web of Science ®Google Scholar
• Radich JP, Kopecky KJ, Appelbaum FR, et al. A randomized trial of dasatinib 100 mg vs imatinib 400 mg in newly diagnosed chronic phase chronic myeloid leukemia. Blood 2012;120:3898–3905.
   PubMed Web of Science ®Google Scholar
• Cortes JE, Kim DW, Kantarjian HM, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol 2012;30:3486–3492.
   PubMed Web of Science ®Google Scholar
• Buchdunger E, Zimmermann J, Mett H, et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 1996;56:100–104.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Kim D-W, Issaragrisil S, et al. Enestnd 4-year (y) update: continued superiority of nilotinib vs imatinib in patients (pts) with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP). Blood 2012;120(Suppl. 1): Abstract 1676.
   Google Scholar
• Alvarado Y, Kantarjian H, O’Brien S, et al. Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase. Cancer 2009;115:3709–3718.
   PubMed Web of Science ®Google Scholar
• Hanfstein B, Muller MC, Hehlmann R, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 2012;26:2096–2102.
   PubMed Web of Science ®Google Scholar
• Hughes TP, Hochhaus A, Branford S, 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.
   PubMed Web of Science ®Google Scholar
• Jabbour E, Kantarjian H, O’Brien S, et al. The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood 2011;118: 4541–4546; quiz 4759.
   PubMed Web of Science ®Google Scholar
• Marin D, Ibrahim AR, Lucas C, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol 2012;30:232–238.
   PubMed Web of Science ®Google Scholar
• Marin D, Milojkovic D, Olavarria E, et al. European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood 2008;112:4437–4444.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Kantarjian H, Jones D, et al. Delayed achievement of cytogenetic and molecular response is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving high-dose or standard-dose imatinib therapy. Blood 2009;113:6315–6321.
   PubMed Web of Science ®Google Scholar
• Fava C, Kantarjian HM, Jabbour E, et al. Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase. Blood 2009;113:5058–5063.
   PubMed Web of Science ®Google Scholar
• Piazza RG, Magistroni V, Franceschino A, et al. The achievement of durable complete cytogenetic remission in late chronic and accelerated phase patients with CML treated with imatinib mesylate predicts for prolonged response at 6 years. Blood Cells Mol Dis 2006;37:111–115.
   PubMed Web of Science ®Google Scholar
• Hochhaus A, Guilhot F, Al-Ali KH, et al. Early BCR-ABL transcript levels predict future molecular response and long-term outcomes in newly diagnosed patients with chronic myeloid leukemia in chronic phase: analysis of ENESTnd 3-year data [Abstract 0584]. Presented at the 17th Congress of the European Hematology Association, 14–17 June 2012, Amsterdam, The Netherlands.
   Google Scholar
• Hochhaus A, Boqué C, Bradley Garelik M, et al. Molecular response kinetics and BCR-ABL reductions in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) receiving dasatinib vs imatinib: DASISION 3-year follow-up [Abstract 0192]. Presented at the 17th Congress of the European Hematology Association, 14–17 June 2012, Amsterdam, The Netherlands.
   Google Scholar
• Jabbour E, Cortes J, Santos FP, et al. Results of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia patients who failed tyrosine kinase inhibitors after developing BCR-ABL1 kinase domain mutations. Blood 2011;117: 3641–3647.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Kantarjian H, O’Brien S, et al. Outcome of patients with chronic myeloid leukemia with multiple ABL1 kinase domain mutations receiving tyrosine kinase inhibitor therapy. Haematologica 2011;96:918–921.
   PubMed Web of Science ®Google Scholar
• Soverini S, Martinelli G, Rosti G, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol 2005;23:4100–4109.
   PubMed Web of Science ®Google Scholar
• 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;102:276–283.
   PubMed Web of Science ®Google Scholar
• Weisberg E, Manley PW, Cowan-Jacob SW, et al. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 2007;7:345–356.
   PubMed Web of Science ®Google Scholar
• Hochhaus A, Saglio G, Larson RA, et al. Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood 2013;121:3703–3708.
   PubMed Web of Science ®Google Scholar
• Fabarius A, Leitner A, Hochhaus A, et al. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood 2011;118:6760–6768.
   PubMed Web of Science ®Google Scholar
• Verma D, Kantarjian H, Shan J, et al. Survival outcomes for clonal evolution in chronic myeloid leukemia patients on second generation tyrosine kinase inhibitor therapy. Cancer 2010;116:2673–2681.
   PubMed Web of Science ®Google Scholar
• Hasford J, Pfirrmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst 1998;90: 850–858.
   PubMed Web of Science ®Google Scholar
• Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 1984;63: 789–799.
   PubMed Web of Science ®Google Scholar
• Oyekunle AA, Osho PO, Aneke JC, et al. The predictive value of the Sokal and Hasford scoring systems in chronic myeloid leukaemia in the imatinib era. J Hematol Malign 2012;2:25–32.
   Google Scholar
• Hasford J, Baccarani M, Hoffmann V, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 2011;118:686–692.
   PubMed Web of Science ®Google Scholar
• Hoffmann VS, Baccarani M, Lindoerfer D, et al. The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib. Leukemia 2013 June 11. [Epub ahead of print]
   Web of Science ®Google Scholar
• Uz B, Buyukasik Y, Atay H, et al. EUTOS CML prognostic scoring system predicts ELN-based “event-free survival” better than Euro/Hasford and Sokal systems in CML patients receiving front-line imatinib mesylate. Hematology 2013;18:247–252.
   PubMed Web of Science ®Google Scholar
• Marin D, Ibrahim AR, Goldman JM. European Treatment and Outcome Study (EUTOS) score for chronic myeloid leukemia still requires more confirmation. J Clin Oncol 2011;29:3944–3945.
   PubMed Web of Science ®Google Scholar
• Sprycel (dasatinib) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co.; 2011.
   Google Scholar
• Gleevec (imatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2012.
   Google Scholar
• Tasigna (nilotinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2012.
   Google Scholar
• Bosulif (bosutinib) [prescribing information]. New York, NY: Pfizer Laboratories; 2012.
   Google Scholar
• Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med 2012;367:2075–2088.
   PubMed Web of Science ®Google Scholar
• Radich JP. The biology of CML blast crisis. Hematology Am Soc Hematol Educ Program 2007:384–391.
   Google Scholar
• Kantarjian HM, O’Brien S, Cortes JE, et al. Treatment of Philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate. Clin Cancer Res 2002;8:2167–2176.
   PubMed Web of Science ®Google Scholar
• Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002;99:1928–1937.
   PubMed Web of Science ®Google Scholar
• Palandri F, Castagnetti F, Alimena G, et al. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up. Haematologica 2009;94:205–212.
   PubMed Web of Science ®Google Scholar
• Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001;344:1038–1042.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Cortes J, O’Brien S, et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood 2002;99:3547–3553.
   PubMed Web of Science ®Google Scholar
• Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 2002;99:3530–3539.
   PubMed Web of Science ®Google Scholar
• Sureda A, Carrasco M, de Miguel M, et al. Imatinib mesylate as treatment for blastic transformation of Philadelphia chromosome positive chronic myelogenous leukemia. Haematologica 2003;88:1213–1220.
   PubMed Web of Science ®Google Scholar
• Palandri F, Castagnetti F, Testoni N, et al. Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up. Haematologica 2008;93: 1792–1796.
   PubMed Web of Science ®Google Scholar
• le Coutre P, Ottmann OG, Giles F, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood 2008;111:1834–1839.
   PubMed Web of Science ®Google Scholar
• Giles FJ, Abruzzese E, Rosti G, et al. Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy. Leukemia 2010;24:1299–1301.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006;354:2542–2551.
   PubMed Web of Science ®Google Scholar
• Nicolini FE, Masszi T, Shen Z, et al. Expanding Nilotinib Access in Clinical Trials (ENACT), an open-label multicenter study of oral nilotinib in adult patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase or blast crisis. Leuk Lymphoma 2012;53:907–914.
   PubMed Web of Science ®Google Scholar
• Giles FJ, Kantarjian HM, le Coutre PD, et al. Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase. Leukemia 2012;26:959–962.
   PubMed Web of Science ®Google Scholar
• Guilhot F, Apperley J, Kim DW, et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood 2007;109:4143–4150.
   PubMed Web of Science ®Google Scholar
• Apperley JF, Cortes JE, Kim DW, et al. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START A trial. J Clin Oncol 2009;27:3472–3479.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, Cortes J, Kim DW, et al. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood 2009;113:6322–6329.
   PubMed Web of Science ®Google Scholar
• Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006;354:2531–2541.
   PubMed Web of Science ®Google Scholar
• Cortes J, Rousselot P, Kim DW, et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 2007;109:3207–3213.
   PubMed Web of Science ®Google Scholar
• Cortes J, Kim DW, Raffoux E, et al. Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase. Leukemia 2008;22:2176–2183.
   PubMed Web of Science ®Google Scholar
• Saglio G, Hochhaus A, Goh YT, et al. Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study: efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily. Cancer 2010;116:3852–3861.
   PubMed Web of Science ®Google Scholar
• 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;16:401–412.
   PubMed Web of Science ®Google Scholar
• Cortes JE, Kim DW, Pinilla-Ibarz J, et al. PACE: a pivotal phase II trial of ponatinib in patients with CML and Ph+ ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. J Clin Oncol 2012;30(Suppl.) Abstract:6503.
   Google Scholar
• Eide CA, Adrian LT, Tyner JW, et al. The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile. Cancer Res 2011;71:3189–3195.
   PubMed Web of Science ®Google Scholar
• Cortes JE, Talpaz M, Kantarjian HM, et al. A phase 1 study of DCC-2036, a novel oral inhibitor of BCR-ABL kinase, in patients with Philadelphia chromosome positive (Ph+) leukemias including patients with T315I mutation. Blood 2011;118(Suppl. 1): Abstract 601.
   Google Scholar
• National Cancer Institute. SEER Stat Fact Sheets: Chronic Myeloid Leukemia. Available from: http://seer.cancer.gov/statfacts/html/cmyl.html
   Google Scholar
• Saussele S, Lauseker M, Gratwohl A, et al. Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood 2010;115:1880–1885.
   PubMed Web of Science ®Google Scholar
• Khoury HJ, Kukreja M, Goldman JM, et al. Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis. Bone Marrow Transplant 2012;47:810–816.
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Chronic myelogenous leukemia. Version 1.2013. Available from: http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf
   Google Scholar
• Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27:6041–6051.
   PubMed Web of Science ®Google Scholar
• Soverini S, Hochhaus A, Nicolini FE, et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood 2011;118:1208–1215.
   PubMed Web of Science ®Google Scholar
• Laneuville P, Dilea C, Yin OQ, et al. Comparative in vitro cellular data alone are insufficient to predict clinical responses and guide the choice of BCR-ABL inhibitor for treating imatinib-resistant chronic myeloid leukemia. J Clin Oncol 2010;28:e169–e171; author reply e172.
   PubMed Web of Science ®Google Scholar
• Cervantes F, Rozman M, Rosell J, et al. A study of prognostic factors in blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia. Br J Haematol 1990;76:27–32.
   PubMed Web of Science ®Google Scholar
• Inverardi D, Lazzarino M, Morra E, et al. Extramedullary disease in Ph’-positive chronic myelogenous leukemia: frequency, clinical features and prognostic significance. Haematologica 1990;75:146–148.
   PubMed Web of Science ®Google Scholar
• Wadhwa J, Szydlo RM, Apperley JF, et al. Factors affecting duration of survival after onset of blastic transformation of chronic myeloid leukemia. Blood 2002;99:2304–2309.
   PubMed Web of Science ®Google Scholar
• Bornhauser M, Jenke A, Freiberg-Richter J, et al. CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluid. Ann Hematol 2004;83:401–402.
   PubMed Web of Science ®Google Scholar
• Leis JF, Stepan DE, Curtin PT, et al. Central nervous system failure in patients with chronic myelogenous leukemia lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic leukemia treated with imatinib (STI-571). Leuk Lymphoma 2004;45:695–698.
   PubMed Web of Science ®Google Scholar
• Neville K, Parise RA, Thompson P, et al. Plasma and cerebrospinal fluid pharmacokinetics of imatinib after administration to nonhuman primates. Clin Cancer Res 2004;10:2525–2529.
   PubMed Web of Science ®Google Scholar
• Petzer AL, Gunsilius E, Hayes M, et al. Low concentrations of STI571 in the cerebrospinal fluid: a case report. Br J Haematol 2002;117:623–625.
   PubMed Web of Science ®Google Scholar
• Ravandi F, Jorgensen JL, Thomas DA, et al. Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. Blood 2013;122:1214–1221.
   PubMed Web of Science ®Google Scholar
• Oki Y, Kantarjian HM, Gharibyan V, et al. Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia. Cancer 2007;109:899–906.
   PubMed Web of Science ®Google Scholar
• Verma D, Kantarjian HM, Jones D, et al. Chronic myeloid leukemia (CML) with P190 BCR-ABL: analysis of characteristics, outcomes, and prognostic significance. Blood 2009;114:2232–2235.
   PubMed Web of Science ®Google Scholar
• Fruehauf S, Topaly J, Buss EC, et al. Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis. Cancer 2007;109:1543–1549.
   PubMed Web of Science ®Google Scholar
• Fang B, Li N, Song Y, et al. Standard-dose imatinib plus low-dose homoharringtonine and granulocyte colony-stimulating factor is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis who have failed prior single-agent therapy with imatinib. Ann Hematol 2010;89:1099–1105.
   PubMed Web of Science ®Google Scholar
• Deau B, Nicolini FE, Guilhot J, et al. The addition of daunorubicin to imatinib mesylate in combination with cytarabine improves the response rate and the survival of patients with myeloid blast crisis chronic myelogenous leukemia (AFR01 study). Leuk Res 2011;35:777–782.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Kantarjian H, Garcia-Manero G, et al. A pilot study of imatinib, low-dose cytarabine and idarubicin for patients with chronic myeloid leukemia in myeloid blast phase. Leuk Lymphoma 2007;48:283–289.
   PubMed Web of Science ®Google Scholar