Current treatment options for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

References

• Ottmann OG, Wassmann B. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2005;118–122.
   PubMedGoogle Scholar
• Radich JP. Philadelphia chromosome-positive acute lymphocytic leukemia. Hematol Oncol Clin North Am 2001;15:21–36.
   PubMed Web of Science ®Google Scholar
• Lazarus HM, Richards SM, Chopra R, et al Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993. Blood 2006;108:465–472.
   PubMed Web of Science ®Google Scholar
• Pfeifer H, Wassmann B, Hofmann WK, et al Risk and prognosis of central nervous system leukemia in patients with Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate. Clin Cancer Res 2003;9:4674–4681.
   PubMed Web of Science ®Google Scholar
• Avivi I, Goldstone AH. Bone marrow transplant in Ph+ ALL patients. Bone Marrow Transplant 2003;31:623–632.
   PubMed Web of Science ®Google Scholar
• de Labarthe A, Rousselot P, Huguet-Rigal F, et al for Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL).Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 2007;109:1408–1413.
   PubMed Web of Science ®Google Scholar
• Lee KH, Lee JH, Choi SJ, et al Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Leukemia 2005;19:1509–1516.
   PubMed Web of Science ®Google Scholar
• Lee S, Kim YJ, Min CK, et al The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 2005;105:3449–3457.
   PubMed Web of Science ®Google Scholar
• Ottmann OG, Wassmann B, Pfeifer H, et al Imatinib given concurrently with induction chemotherapy is superior to imatinib subsequent to induction and consolidation in newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (PH+ALL) [abstract]. Blood 2004;104(Suppl.): (Abstract 685).
   Google Scholar
• Thomas DA, Faderl S, Cortes J, et al Outcome with the hyper-CVAD and imatinib mesylate regimen in Philadelphia (Ph) positive acute lymphocytic leukemia (ALL) [abstract]. Blood 2005;106(Suppl.): (Abstract 1830).
   Google Scholar
• Yanada M, Takeuchi J, Sugiura I, et al High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 2006;24:460–466.
   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
• Ottmann OG, Druker BJ, Sawyers CL, et al A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 2002;100:1965–1971.
   PubMed Web of Science ®Google Scholar
• Alvarado Y, Apostolidou E, Swords R, Giles F. Emerging therapeutic options for Philadelphia-positive acute lymphocytic leukemia. Expert Opin Emerg Drugs 2007;1:165–179.
   Web of Science ®Google Scholar
• Dombret H, Gabert J, Boiron JM, et al Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia – results of the prospective multicenter LALA-94 trial. Blood 2002;100:2357–2366.
   PubMed Web of Science ®Google Scholar
• Gleissner B, Gokbuget N, Bartram CR, et al Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 2002;99:1536–1543.
   PubMed Web of Science ®Google Scholar
• Hoelzer D, Gokbuget N. Recent approaches in acute lymphoblastic leukemia in adults. Crit Rev Oncol Hematol 2000;36:49–58.
   PubMed Web of Science ®Google Scholar
• Hoelzer D, Gokbuget N. Treatment of elderly patients with acute lymphoblastic leukemia [abstract]. In: Perry MC, editor. American Society of Clinical Oncology Educational Book. Baltimore, MD: Lippincott Williams and Wilkins; 2002. pp 533–539.
   Google Scholar
• Kantarjian HM, O'Brien S, Smith TL, et al Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 2000;18:547–561.
   PubMed Web of Science ®Google Scholar
• Cataland SR, Daugherty CK, Weseman EC, Larson RA. Preliminary experience with a new chemotherapy regimen for adults with acute lymphoblastic leukemia. Leuk Lymphoma 2001;41:297–307.
   PubMed Web of Science ®Google Scholar
• Thiebaut A, Vernant JP, Degos L, et al Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation. A follow-up report of the French protocol LALA 87. Hematol Oncol Clin North Am 2000;14:1353–1366, x.
   PubMed Web of Science ®Google Scholar
• Fielding AK, Rowe JM, Richards SM, et al Prospective outcome data on 267 unselected adult patients with Philadelphia-chromosome positive acute lymphoblastic leukaemia confirms the superiority of allogeneic transplant over chemotherapy in the pre-imatinib era: results from the international ALL trial MRC UKALLXII/ECOG2993. Blood 2009;113:4489–4496.
   PubMed Web of Science ®Google Scholar
• Barrett AJ, Horowitz MM, Ash RC, et al Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 1992;79:3067–3070.
   PubMed Web of Science ®Google Scholar
• Sierra J, Radich J, Hansen JA, et al Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 1997;90:1410–1414.
   PubMed Web of Science ®Google Scholar
• Snyder DS, Nademanee AP, O'Donnell MR, et al Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission. Leukemia 1999;13:2053–2058.
   PubMed Web of Science ®Google Scholar
• Thomas X, Boiron JM, Huguet F, et al Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004;22:4075–4086.
   PubMed Web of Science ®Google Scholar
• Cornelissen JJ, Carston M, Kollman C, et al Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood 2001;97:1572–1577.
   PubMed Web of Science ®Google Scholar
• Marks DI, Aversa F, Lazarus HM. Alternative donor transplants for adult acute lymphoblastic leukaemia: a comparison of the three major options. Bone Marrow Transplant 2006;38:467–475.
   PubMed Web of Science ®Google Scholar
• Martin H, Atta J, Klein SA, et al Autologous BMT/PBSCT in 40 patients with bcr-abl positive acute lymphoblastic leukemia: long-term follow-up of a GMALL study [abstract]. Hematol J 2001;I: Abstract 187.
   Google Scholar
• Druker BJ, Talpaz M, Resta DJ, et al Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031–1037.
   PubMed Web of Science ®Google Scholar
• Thomas DA, Faderl S, Cortes J, et al Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 2004;103:4396–4407.
   PubMed Web of Science ®Google Scholar
• Ottmann O, Dombret H, Martinelli G, et al Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood 2007;110:2309–2315.
   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
• Larson R, Ottmann O, Kantarjian H, et al A phase II study of nilotinib administered to imatinib resistant or intolerant patients with chronic myelogenous leukemia (CML) in blast crisis (BC) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL) [abstract]. J Clin Oncol 2007;25(Suppl. 8): (Abstract 7040).
   Google Scholar
• Delannoy A, Delabesse E, Lheritier V, et al Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study. Leukemia 2006;20:1526–1532.
   PubMed Web of Science ®Google Scholar
• Ottmann O, Wassmann B, Pfeifer H, et al Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Cancer 2007;109:2068–2076.
   PubMed Web of Science ®Google Scholar
• Vignetti M, Fazi P, Meloni G, et al Dramatic improvement in CR rate and CR duration with imatinib in adult and elderly Ph+ ALL patients: results of the GIMEMA prospective study LAL0201 [abstract]. Blood 2004;104(Suppl.): (Abstract 2739).
   Google Scholar
• Fielding AK, Richards SM, Lazarus HM, et al Does imatinib change the outcome in Philadelphia chromosome-positive acute lymphoblastic leukaemia in adults? Data from the UKALLXII/ECOG2993 study [abstract]. Blood 2007;110(Suppl.): (Abstract 8).
   PubMed Web of Science ®Google Scholar
• Thomas DA, Kantarjian HM, Cortes J, et al Outcome after frontline therapy with the hyper-CVAD and imatinib mesylate regimen for adults with de novo or minimally treated Philadelphia chromosome (Ph) positive acute lymphocytic leukemia (ALL) [abstract]. Blood 2008;112(Suppl.): (Abstract 2931).
   Google Scholar
• Schultz KR, Bowman P, Slayton W, et al Improved early event free survival (EFS) in children with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) with intensive imatinib in combination with high dose chemotherapy: Children's Oncology Group (COG) Study AALL0031 [abstract]. Blood 2007;110(Suppl.): (Abstract 4).
   PubMed Web of Science ®Google Scholar
• Gleissner B, Rieder H, Thiel E, et al Prospective BCR-ABL analysis by polymerase chain reaction (RT-PCR) in adult acute B-lineage lymphoblastic leukemia: reliability of RT-nested-PCR and comparison to cytogenetic data. Leukemia 2001;15:1834–1840.
   PubMed Web of Science ®Google Scholar
• Lee S, Kim DW, Cho B, et al Risk factors for adults with Philadelphia-chromosome-positive acute lymphoblastic leukaemia in remission treated with allogeneic bone marrow transplantation: the potential of real-time quantitative reverse-transcription polymerase chain reaction. Br J Haematol 2003;120:145–153.
   PubMed Web of Science ®Google Scholar
• Mitterbauer G, Nemeth P, Wacha S, et al Quantification of minimal residual disease in patients with BCR-ABL-positive acute lymphoblastic leukaemia using quantitative competitive polymerase chain reaction. Br J Haematol 1999;106:634–643.
   PubMed Web of Science ®Google Scholar
• Radich J, Gehly G, Lee A, et al Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation. Blood 1997;89:2602–2609.
   PubMed Web of Science ®Google Scholar
• Stirewalt DL, Guthrie KA, Beppu L, et al Predictors of relapse and overall survival in Philadelphia chromosome-positive acute lymphoblastic leukemia after transplantation. Biol Blood Marrow Transplant 2003;9:206–212.
   PubMed Web of Science ®Google Scholar
• Wassmann B, Pfeifer H, Stadler M, et al Early molecular response to post-transplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 2005;106:458–463.
   PubMed Web of Science ®Google Scholar
• Yanada M, Sugiura I, Takeuchi J, et al Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy. Br J Haematol 2008;143:503–510.
   PubMed Web of Science ®Google Scholar
• 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;108:28–37.
   PubMed Web of Science ®Google Scholar
• Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005;105:2640–2653.
   PubMed Web of Science ®Google Scholar
• Hofmann WK, Komor M, Hoelzer D, Ottmann OG. Mechanisms of resistance to STI571 (Imatinib) in Philadelphia-chromosome positive acute lymphoblastic leukemia. Leuk Lymphoma 2004;45:655–660.
   PubMed Web of Science ®Google Scholar
• Soverini S, Colarossi S, Gnani A, et al on behalf of GIMEMA Working Party on Chronic Myeloid Leukemia. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA working party on chronic myeloid leukemia. Clin Cancer Res 2006;12:7374–7379.
   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
• 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
• Pfeifer H, Wassmann B, Pavlova A, et al Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 2007;110:727–734.
   PubMed Web of Science ®Google Scholar
• Illmer T, Schaich M, Platzbecker U, et al P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 2004;18:401–408.
   PubMed Web of Science ®Google Scholar
• Mahon FX, Deininger MW, Schultheis B, et al Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood 2000;96:1070–1079.
   PubMed Web of Science ®Google Scholar
• Thomas J, Wang L, Clark RE, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood 2004;104:3739–3745.
   PubMed Web of Science ®Google Scholar
• White DL, Saunders VA, Dang P, et al OCT-1 mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107); reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood 2006;108:697–704.
   PubMed Web of Science ®Google Scholar
• Hochhaus A, La Rosee P. Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia 2004;18:1321–1331.
   PubMed Web of Science ®Google Scholar
• Dai Y, Rahmani M, Corey SJ, Dent P, Grant S. A Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2. J Biol Chem 2004;279:34227–34239.
   PubMed Web of Science ®Google Scholar
• Donato NJ, Wu JY, Stapley J, et al BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 2003;101:690–698.
   PubMed Web of Science ®Google Scholar
• Hu Y, Swerdlow S, Duffy TM, Weinmann R, Lee FY, Li S. Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. Proc Natl Acad Sci USA 2006;103:16870–16875.
   PubMed Web of Science ®Google Scholar
• Klejman A, Schreiner SJ, Nieborowska-Skorska M, et al The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells. EMBO J 2006;21:5766–5774.
   Web of Science ®Google Scholar
• Meyn MA, III, Wilson MB, Abdi FA, et al Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and modulate Bcr-Abl transforming activity. J Biol Chem 2006;281:30907–30916.
   PubMed Web of Science ®Google Scholar
• Ptasznik A, Urbanowska E, Chinta S, et al Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. J Exp Med 2002;196:667–678.
   PubMed Web of Science ®Google Scholar
• Ptasznik A, Nakata Y, Kalota A, Emerson SG, Gewirtz AM. Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells. Nat Med 2004;10:1187–1189.
   PubMed Web of Science ®Google Scholar
• Tanis KQ, Veach D, Duewel HS, Bornmann WG, Koleske AJ. Two distinct phosphorylation pathways have additive effects on Abl family kinase activation. Mol Cell Biol 2003;23:3884–3896.
   PubMed Web of Science ®Google Scholar
• Tipping AJ, Baluch S, Barnes DJ, et al Efficacy of dual-specific Bcr-Abl and Src-family kinase inhibitors in cells sensitive and resistant to imatinib mesylate. Leukemia 2004;18:1352–1356.
   PubMed Web of Science ®Google Scholar
• Engelman A, Rosenberg N. Bcr/abl and src but not myc and ras replace v-abl in lymphoid transformation. Mol Cell Biol 1990;10:4365–4369.
   PubMed Web of Science ®Google Scholar
• Hu Y, Liu Y, Pelletier S, et al Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet 2004;36:453–461.
   PubMed Web of Science ®Google Scholar
• Li S. Src kinases as targets for B cell acute lymphoblastic leukaemia therapy. Expert Opin Ther Targets 2005;9:329–341.
   PubMed Web of Science ®Google Scholar
• Wilson MB, Schreiner SJ, Choi HJ, Kamens J, Smithgall TE. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis. Oncogene 2002;21:8075–8088.
   PubMed Web of Science ®Google Scholar
• O'Hare T, Walters DK, Stoffregen EP, et al In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 2005;65:4500–4505.
   PubMed Web of Science ®Google Scholar
• Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305:399–401.
   PubMed Web of Science ®Google Scholar
• Tokarski JS, Newitt JA, Chang CY, et al The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res 2006;66:5790–5797.
   PubMed Web of Science ®Google Scholar
• Azam M, Nardi V, Shakespeare WC, et al Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proc Natl Acad Sci USA 2006;103:9244–9249.
   PubMed Web of Science ®Google Scholar
• Burgess MR, Skaggs BJ, Shah NP, Lee FY, Sawyers CL. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci USA 2005;102:3395–3400.
   PubMed Web of Science ®Google Scholar
• Soverini S, Colarossi S, Gnani A, et al Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain. Haematologica 2007;92:401–404.
   PubMed Web of Science ®Google Scholar
• Larson RA, Ottmann OG, Shah NP, et al Dasatinib 140 mg once daily (QD) has equivalent efficacy and improved safety compared with 70 mg twice daily (BID) in patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL): 2-year data from CA180-035 [abstract]. Blood 2008;112(Suppl.): (Abstract 2926).
   Google Scholar
• Koskenvesa P, Rimpilainen J, Lundan T, et al Dasatinib is an effective treatment of central nervous system Ph-positive leukemia [abstract]. Haematologica 2007;92(Suppl. 2): (Abstract 0315).
   Google Scholar
• Wild R, Castaneda S, Flefleh C, et al BMS-354825, a dual SRC/ABL kinase inhibitor, displays potent anti-tumor activity in a model of intracranial CML growth [abstract]. Blood 2004;104(Suppl.): (Abstract 1988).
   Google Scholar
• Dai H, Marbach P, Lemaire M, Hayes M, Elmquist WF. Distribution of STI-571 to the brain is limited by P-glycoprotein-mediated efflux. J Pharmacol Exp Ther 2003;304:1085–1092.
   PubMed Web of Science ®Google Scholar
• Foa R, Vitale A, Guarini A, et al Line treatment of adult Ph+ acute lymphoblastic leukemia (ALL) patients. Final results of the GIMEMA LAL1205 study [abstract]. Blood 2008;112(Suppl.): (Abstract 305).
   Google Scholar
• Ravandi F, Thomas D, Kantarjian H, et al Phase II study of combination of hyperCVAD with dasatinib in frontline therapy of patients with Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia (ALL) [abstract]. Blood 2008;112(Suppl.): (Abstract 2921).
   Google Scholar
• Rousselot P, Cayuela J-M, Recher C, et al Dasatinib (Sprycel®) and chemotherapy for first-line treatment in elderly patients with de novo Philadelphia positive ALL: results of the first 22 patients included in the EWALL-Ph-01 trial (on behalf of the European Working Group on Adult ALL [EWALL]) [abstract]. Blood 2008;112(Suppl.): (Abstract 2920).
   Google Scholar
• Jabbour E, O'Brien S, Thomas DA, et al Combination of the hyperCVAD regimen with dasatinib is effective in patients with relapsed Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia (ALL) and lymphoid blast phase chronic myeloid leukemia (CML-LB) [abstract]. Blood 2008;112(Suppl.): (Abstract 2919).
   Google Scholar
• Jensen MR, Bruggen J, Dilea C, Mestan J, Manley PW. AMN107: efficacy of the selective Bcr-Abl tyrosine kinase inhibitor in a murine model of chronic myelogenous leukemia [abstract]. Proc Am Assoc Cancer Res 2006;47: (Abstract 261).
   Google Scholar
• Weisberg E, Manley PW, Breitenstein W, et al Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 2005;7:129–141.
   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
• Golas JM, Arndt K, Etienne C, et al SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res 2003;63:375–381.
   PubMed Web of Science ®Google Scholar
• Kimura S, Naito H, Segawa H, et al NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood 2005;3948–3954.
   PubMed Web of Science ®Google Scholar
• Naito H, Kimura S, Nakaya Y, et al In vivo antiproliferative effect of NS-187, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor, on leukemic cells harbouring Abl kinase domain mutations. Leuk Res 2006;30:1443–1446.
   PubMed Web of Science ®Google Scholar
• Gambacorti-Passarini C, Pogliani EM, Baccarani M, et al Bosutinib (SKI-606) demonstrates clinical activity and is well tolerated in patients with AP and BP CML and Ph+ ALL [abstract]. Blood 2008;112(Suppl.): (Abstract 1101).
   Google Scholar
• Carter TA, Wodicka LM, Shah NP, et al Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci USA 2005;102:11011–11016.
   PubMed Web of Science ®Google Scholar
• Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman SJ. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood 2007;109:500–502.
   PubMed Web of Science ®Google Scholar
• Harrington EA, Bebbington D, Moore J, et al VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo.Nat Med 2004;10:262–267.
   PubMed Web of Science ®Google Scholar
• Young MA, Shah NP, Chao LH, et al Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res 2006;66:1007–1014.
   PubMed Web of Science ®Google Scholar
• de Lavallade H, Khorashad JS, Davis HP, et al Interferon-{α} or homoharringtonine as salvage treatment for chronic myeloid leukemia patients who acquire the T315I BCR-ABL mutation. Blood 2007;110:2779–2780.
   PubMed Web of Science ®Google Scholar
• Nimmanapalli R, Fuino L, Bali P, et al Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or -refractory chronic myelogenous leukemia-blast crisis cells. Cancer Res 2003;63:5126–5135.
   PubMed Web of Science ®Google Scholar
• Mullighan CG, Millrt CB, Radtke I, et al BCR-ABL1 lymphoblastic leukemia is characterized by the deletion of Ikaros. Nature 2008;453:110–115.
   PubMed Web of Science ®Google Scholar
• Wassmann B, Pfeifer H, Scheuring UJ, et al Early prediction of response in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) treated with imatinib. Blood 2004;103:1495–1498.
   PubMed Web of Science ®Google Scholar