Novel targeted therapies in acute lymphoblastic leukemia

Leukemia and Lymphoma

Volumn 55, Issue 4, 2014, Pages 737-748

  Portell, Craig A ^a   Advani, Anjali S ^a  

^a TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

Acute lymphoblastic leukemia; Alemtuzumab; Blinatumomab; Bortezomib; Chimeric antigen receptor therapy; Decitabine; Epratuzumab; Inotuzumab ozogamicin; NOTCH1; Rituximab

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ALEMTUZUMAB; ANTINEOPLASTIC AGENT; BLINATUMOMAB; BORTEZOMIB; BRUTON TYROSINE KINASE INHIBITOR; CD135 ANTIGEN; EPRATUZUMAB; GAMMA SECRETASE INHIBITOR; INOTUZUMAB OZOGAMICIN; LESTAURTINIB; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; NOTCH1 RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEASOME; QUIZARTINIB; RITUXIMAB; VINCRISTINE SULFATE; LIPOSOME; LYMPHOCYTE ANTIGEN RECEPTOR; MONOCLONAL ANTIBODY; PROTEASOME INHIBITOR; PROTEIN KINASE INHIBITOR;

ABSENCE OF SIDE EFFECTS; ACUTE LYMPHOBLASTIC LEUKEMIA; B CELL LEUKEMIA; BONE MARROW SUPPRESSION; BRAIN DISEASE; CANCER PATIENT; CYTOKINE RELEASE SYNDROME; CYTOMEGALOVIRUS INFECTION; DIARRHEA; DNA METHYLATION; DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; EMPYEMA; FEVER; HERPES SIMPLEX; HERPES ZOSTER; HUMAN; HYPERBILIRUBINEMIA; HYPOTENSION; LEUKEMIA RELAPSE; NAUSEA; NEUROPATHY; NEUTROPENIA; PRIORITY JOURNAL; REVIEW; SEIZURE; SIDE EFFECT; THROMBOCYTOPENIA; TREATMENT OUTCOME; VOMITING; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; GENETICS; METABOLISM; MOLECULARLY TARGETED THERAPY; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; DNA METHYLATION; FMS-LIKE TYROSINE KINASE 3; HUMANS; LIPOSOMES; MOLECULAR TARGETED THERAPY; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROTEASOME INHIBITORS; PROTEIN KINASE INHIBITORS; RECEPTOR, NOTCH1; RECEPTORS, ANTIGEN, B-CELL; RECEPTORS, ANTIGEN, T-CELL;

EID: 84904354628     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.3109/10428194.2013.823493     Document Type: Review

References (104)

1. Schrappe M, Reiter A, Ludwig WD, et al. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. Blood 2000;95: 3310-3322. (Pubitemid 30428458)
2. Silverman LB, Gelber RD, Dalton VK, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood 2001;97:1211-1218. (Pubitemid 32183741)
3. Stock W, Johnson JL, Stone RM, et al. Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia: results of Cancer and Leukemia Group B Study 19802. Cancer 2013;119:90-98.
4. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 2005;106:3760-3767. (Pubitemid 41739010)
5. Thomas DA, O'Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol 2010;28:3880-3889.
6. Ribera J-M. Optimal approach to treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: how to best use all the available tools. Leuk Lymphoma 2013;54:21-27.
7. Paietta E, Li X, Richards S, et al. Implications for the use of monoclonal antibodies in future adult ALL trials: analysis of antigen expression in 505 B-lineage (B-Lin) ALL patients (pts) on the MRC UKALLXII/ECOG2993 intergroup trial. Blood 2008;112(Suppl. 1): Abstract 1907.
8. Raponi S, De Propris MS, Intoppa S, et al. Flow cytometric study of potential target antigens (CD19, CD20, CD22, CD33) for antibody- based immunotherapy in acute lymphoblastic leukemia:analysis of 552 cases. Leuk Lymphoma 2011;52:1098-1107.
9. Thomas DA, O'Brien S, Jorgensen JL, et al. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood 2009; 113: 6330-6337.
10. Dworzak MN, Schumich A, Printz D, et al. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy.Blood 2008; 112: 3982-3988.
11. Kennedy AD, Beum PV Solga MD, et al. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J Immunol 2004; 172: 3280-3288. (Pubitemid 38263720)
12. Stockmeyer B, Dechant M, van Egmond M, et al. Triggering Fc alpha-receptor I (CD89) recruits neutrophils as effector cells for CD20- directed antibody therapy. J Immunol 2000;165:5954-5961.
13. Thomas DA, Kantarjian HM, Jorgensen JL, et al. Outcomes continue to be favorable for de novo Philadelphia chromosome negative B-lymphoblastic leukemia (ALL) after therapy with Hyper- CVAD (with or without rituximab) regimen. Blood 2012;120:(Suppl. 1): Abstract 3572.
14. Hoelzer D, Huettmann A, Kaul F, et al. Immunochemotherapy with rituximab improves molecular CR rate and outcome in CD20 + B-lineage standard and high risk patients; results of 263 CD20 + patients studied prospectively in GMALL study 07/2003. Blood 2010;116(Suppl. 1): Abstract 170.
15. Briiggemann M, Raff T, Flohr T, et al. Clinical significance of minimal residual disease quantification in adult patients with standard- risk acute lymphoblastic leukemia. Blood 2006; 107: 1116-1123. (Pubitemid 43156313)
16. Poe JC, Fujimoto Y, Hasegawa M, et al. CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms. Nat Immunol 2004; 5: 1078-1087. (Pubitemid 41057728)
17. Carnahan J, Stein R, Qu Z, et al. Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab. Mol Immunol 2007;44:1331-1341. (Pubitemid 44415959)
18. RaetzEA, BorowitzMJ, DevidasM, et al. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: a Children's Oncology Group Study [corrected].J Clin Oncol 2008; 26: 3971-3978.
19. Raetz EA, Cairo MS, Borowitz MJ, et al. Reinduction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL) in children, adolescents and young adults: results from Children's Oncology Group (COG) study ADVL04P2. Blood 2011;118 (Suppl.): Abstract 573.
20. Advani A, McDonough S, Coutre S, et al. Southwest Oncology Group study S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukemia. Blood 2012;120(Suppl. 1): Abstract 2603.
21. Advani AS, Gundacker HM, Sala-Torra O, et al. Southwest Oncology Group Study S0530: a phase 2 trial of clofarabine and cytarabine for relapsed or refractory acute lymphocytic leukaemia. Br J Haematol 2010; 151: 430-434.
22. Tibes R, Keating MJ, Ferrajoli A, et al. Activity of alemtuzumab in patients with CD52-positive acute leukemia. Cancer 2006;106: 2645-2651.
23. Hu Y, Turner MJ, Shields J, et al. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology 2009; 128: 260-270.
24. Angiolillo AL, Yu AL, Reaman G, et al. A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children's Oncology Group report. Pediatr Blood Cancer 2009; 53: 978-983.
25. Stock W, Sanford B, Lozanski G, et al. Alemtuzumab can be incorporated into front-line therapy of adult acute lymphoblastic leukemia (ALL): final phase I results of a Cancer and Leukemia Group B Study (CALGB 10102). Blood 2009;114(Suppl. 1): Abstract 838.
26. Stock W, Yu D, Sanford B, et al. Incorporation of alemtuzumab into front-line therapy of adult acute lymphoblastic leukemia (ALL) is feasible: a phase I/II study from the Cancer and Leukemia Group B (CALGB 10102). Blood 2005;106(Suppl. 1): Abstract 145.
27. Carnahan J, Wang P, Kendall R, et al. Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of in vitro properties. Clin Cancer Res 2003;9:3982S-3990S.
28. de Vries JF, Zwaan CM, De Bie M, et al. The novel calicheamicin- conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells. Leukemia 2012; 26: 255-264.
29. DiJoseph JF, Armellino DC, Boghaert ER, et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies.Blood 2004;103:1807-1814. (Pubitemid 38268977)
30. Jabbour E, O'Brien S, Thomas D, et al. Inotuzumab ozogamicin (IO; CMC544), a CD22 monoclonal antibody attached to calicheamycin, produces complete response (CR) plus complete marrow response (mCR) of greater than 50% in refractory relapse (R-R) acute lymphocytic leukemia (ALL). J Clin Oncol 2011;29(Suppl.): Abstract 6507.
31. Kantarjian H, Thomas D, Jorgensen J, et al. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol 2012;13:403-411.
32. Advani A, Coiffier B, Czuczman MS, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. J Clin Oncol 2010;28:2085-2093.
33. DeAngelo D, Stock W, Petersdorf S, et al. Weekly inotuzumab ozogamicin in adult patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia. Blood 2012;120(Suppl. 1): Abstract 2612.
34. O'Brien S, Thomas DA, Jorgensen JL, et al. Experience with 2 dose schedules of inotuzumab ozogamicin, single dose, and weekly, in refractory-relapsed acute lymphocytic leukemia (ALL). Blood 2012;120(Suppl. 1): Abstract 671.
35. Hoffmann P, Hofmeister R, Brischwein K, et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int J Cancer 2005;115:98-104. (Pubitemid 40559673)
36. Loffler A, Kufer P, Lutterbiise R, et al. A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 2000; 95: 2098-2103. (Pubitemid 30151651)
37. Gabrilovich D, PisarevV. Tumor escape from immune response: mechanisms and targets of activity. Curr Drug Targets 2003;4:525-536. (Pubitemid 37139048)
38. Dreier T, Lorenczewski G, Brandl C, et al. Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer 2002; 100: 690-697. (Pubitemid 34832980)
39. Brandl C, Haas C, d'Argouges S, et al. The effect ofdexamethasone on polyclonal T cell activation and redirected target cell lysis as induced by a CD19/CD3-bispecific single-chain antibody construct. Cancer Immunol Immunother 2007;56:1551-1563. (Pubitemid 47094384)
40. Klinger M, Brandl C, Zugmaier G, et al. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood 2012;119:6226-6233.
41. Nagorsen D, Kufer P, Baeuerle PA, et al. Blinatumomab: a historical perspective. Pharmacol Ther 2012;136:334-342.
42. Nagorsen D, Bargou R, Ruttinger D, et al. Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab. Leuk Lymphoma 2009; 50: 886-891.
43. Nagorsen D, Baeuerle PA.Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res 2011; 317: 1255-1260.
44. Bargou R, Leo E, Zugmaier G, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 2008; 321: 974-977.
45. Topp MS, Kufer P, Gokbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival.J Clin Oncol 2011; 29: 2493-2498.
46. Topp MS, Goekbuget N, Zugmaier G, et al. Anti-CD19 BiTE blinatumomab induces high complete remission rate and prolongs overall survival in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL).Blood 2012; 120(Suppl. 1): Abstract 670.
47. Topp MS, Gokbuget N, Zugmaier G, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL.Blood 2012; 120: 5185-5187.
48. Fielding AK, Richards SM, Chopra R, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study.Blood 2007; 109: 944-950. (Pubitemid 46220637)
49. Hollyman D, Stefanski J, Przybylowski M, et al. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy.J Immunother 2009; 32: 169-180.
50. Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor- modified T cells in chronic lymphoid leukemia. N Engl J Med 2011; 365: 725-733.
51. Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T-cells rapidly induce molecular remissions in adults with chemotherapy- refractory acute lymphoblastic leukemia. Sci Transl Med 2013;5:177ra38.
52. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor- modified T-cells for acute lymphoid leukemia. N Engl J Med 2013; 368: 1509-1518.
53. Kalos M, Levine BL, Porter DL, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011;3:95ra73.
54. Tanigaki K, Honjo T. Regulation of lymphocyte development by Notch signaling. Nat Immunol 2007;8:451-456. (Pubitemid 46605909)
55. Blaumueller CM, Qi H, Zagouras P, et al. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell 1997;90:281-291. (Pubitemid 27329713)
56. van Tetering G, van Diest P, Verlaan I, et al. Metalloprotease ADAM10 is required for Notch1 site 2 cleavage. J Biol Chem 2009; 284: 31018-31027.
57. De Strooper B, Annaert W, Cupers P, et al. A presenilin- 1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain.Nature 1999; 398: 518-522.
58. Schroeter EH, Kisslinger JA, Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 1998; 393: 382-386. (Pubitemid 28269713)
59. Tzoneva G, Ferrando AA. Recent advances on NOTCH signaling in T-ALL. Curr Top Microbiol Immunol 2012;360:163-182.
60. Fryer CJ, White JB, Jones KA. Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 2004; 16: 509-520. (Pubitemid 39531875)
61. Weng AP, Ferrando AA, Lee W, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004;306:269-271. (Pubitemid 39336870)
62. Groth C, Fortini ME. Therapeutic approaches to modulating Notch signaling: current challenges and future prospects. Semin Cell Dev Biol 2012;23:465-472.
63. Lewis HD, Leveridge M, Strack PR, et al. Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of Notch signaling. Chem Biol 2007;14: 209-219. (Pubitemid 46274429)
64. DeAngelo DJ, Stone RM, Silverman LB, et al. A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias. J Clin Oncol 2006;24(Suppl.): Abstract 6585.
65. Samon JB, Castillo-Martin M, Hadler M, et al. Preclinical analysis of the y-secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia. Mol Cancer Ther 2012;11:1565-1575.
66. Wei P, Walls M, Qiu M, et al. Evaluation of selective gamma- secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther 2010;9:1618-1628.
67. Palomero T, Dominguez M, Ferrando AA. The role of the PTEN/AKT pathway in NOTCH1-induced leukemia. Cell Cycle 2008; 7: 965-970. (Pubitemid 351679827)
68. Palomero T, Sulis ML, Cortina M, et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med 2007;13:1203-1210. (Pubitemid 47530629)
69. Sarmento LM, Barata JT. Therapeutic potential of Notch inhibition in T-cell acute lymphoblastic leukemia: rationale, caveats and promises. Expert Rev Anticancer Ther 2011;11:1403-1415.
70. Silva A, Jotta PY, Silveira AB, et al. Regulation of PTEN by CK2 and Notch1 in primary T-cell acute lymphoblastic leukemia: rationale for combined use of CK2- and gamma-secretase inhibitors. Haematologica 2010; 95: 674-678.
71. Wu P, Hu Y-Z. PI3K/Akt/mTOR pathway inhibitors in cancer: a perspective on clinical progress. Curr Med Chem 2010;17: 4326-4341.
72. Aste-Amezaga M, Zhang N, Lineberger JE, et al. Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors. PloS One 2010; 5: e9094.
73. Wu Y, Cain-Hom C, Choy L, et al. Therapeutic antibody targeting of individual Notch receptors. Nature 2010;464:1052-1057.
74. Chill6nMC, Gomez-CasaresMT, Lopez-Jorge CE, et al. Prognostic significance of FLT3 mutational status and expression levels in MLL- AF4 + and MLL-germline acute lymphoblastic leukemia. Leukemia 2012; 26: 2360-2366.
75. Armstrong SA, Mabon ME, Silverman LB, et al. FLT3 mutations in childhood acute lymphoblastic leukemia. Blood 2004; 103: 3544-3546. (Pubitemid 38525690)
76. ArmstrongSA, Staunton JE, Silverman LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 2002; 30: 41-47.
77. Levis M, Ravandi F, Wang ES, et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 2011;117:3294-3301.
78. Brown P, Levis M, Shurtleff S, et al. FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression.Blood 2005; 105: 812-820. (Pubitemid 40070769)
79. Brown P, Levis M, McIntyre E, et al. Combinations of the FLT3 inhibitor CEP-701 and chemotherapy synergistically kill infant and childhood MLL-rearranged ALL cells in a sequence-dependent manner. Leukemia 2006; 20: 1368-1376. (Pubitemid 44084049)
80. Brown P, Hunger SP, Smith FO, et al. Novel targeted drug therapies for the treatment of childhood acute leukemia. Expert Rev Hematol 2009; 2: 145.
81. Brown P, Hilden JM, Dreyer ZE, et al. Report on excessive induction toxicity in infants with ALL enrolled on COG protocol AALL0631: a Children's Oncology Group study. Blood 2009;114(Suppl. 1): Abstract 3091.
82. Zarrinkar PP, Gunawardane RN, Cramer MD, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood 2009; 114: 2984-2992.
83. Kampa-Schittenhelm KM, Heinrich MC, Akmut F, et al. Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KITisoforms. Mol Cancer 2013;12:19.
84. Cortes JE, Perl AE, Dombret H, et al. Final results of a phase 2 open- label, monotherapy efficacy and safety study of quizartinib (AC220) in patients > = 60 years of age with FLT3 ITD positive or negative relapsed/refractory acute myeloid leukemia. Blood 2012;120(Suppl. 1): Abstract 48.
85. Katz FE, Lovering RC, Bradley LA, et al. Expression of the X-linked agammaglobulinemia gene, btk in B-cell acute lymphoblastic leukemia. Leukemia 1994;8:574-577. (Pubitemid 24133023)
86. Feldhahn N, Rio P, Ndikung B, et al. Deficiency of Bruton's tyrosine kinase in B cell precursor leukemia cells. Proc Natl Acad Sci USA 2005; 102: 13266-13271. (Pubitemid 41325012)
87. Goodman PA, Wood CA, Vassilev AO, et al. Defective expression of Bruton's tyrosine kinase in acute lymphoblastic leukemia. Leuk Lymphoma 2003; 44: 1011-1018. (Pubitemid 36417001)
88. Schult C, Dahlhaus M, Glass A, et al. The dual kinase inhibitor NVP-BEZ235 in combination with cytotoxic durgs exerts anti- proliferative activity towards acute lymphoblastic leukemia. Anticancer Res 2012; 32: 463-474.
89. Gutierrez A, Sanda T, Grebliunaite R, et al. High frequency of PTEN, PI3K and AKT abnormalities in T-cell acute lymphoblastic leukemia. Blood 2009; 114: 647-650.
90. Cortes J, Thomas D, Koller C, et al. Phase I study of bortezomib in refractory or relapsed acute leukemias. Clin Cancer Res 2004; 10: 3371-3376. (Pubitemid 38685442)
91. Horton TM, Pati D, Plon SE, et al. A phase 1 study of the proteasome inhibitor bortezomib in pediatric patients with refractory leukemia: a Children's Oncology Group study. Clin Cancer Res 2007; 13: 1516-1522. (Pubitemid 46450443)
92. Horton TM, Gannavarapu A, Blaney SM, et al. Bortezomib interactions with chemotherapy agents in acute leukemia in vitro. Cancer Chemother Pharmacol 2006; 58: 13-23.
93. Messinger Y, Gaynon P, RaetzE, et al. Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leukemia (TACL) consortium. Pediatr Blood Cancer 2010; 55: 254-259.
94. Messinger YH, Gaynon PS, Sposto R, et al. Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study. Blood 2012;120:285-290.
95. Filicko-O ' Hara J, Mookerjee B, Carabasi MH, et al N. Phase I trial of bortezomib, mitoxantrone and etoposide in relapsed/refractory acute leukemia. J Clin Oncol 2008;26(Suppl.): Abstract 7071.
96. Filicko-O'Hara J, Mookerjee B, Alpdogan O, et al. Phase II study of bortezomib, mitoxantrone and etoposide in relapsed/refractory acute leukemias. Blood 2010;116(Suppl. 1): Abstract 2192.
97. Roman-Gomez J, Jimenez-Velasco A, Barrios M, et al. Poor prognosis in acute lymphoblastic leukemia may relate to promoter hypermethylation of cancer-related genes. Leuk Lymphoma 2007; 48: 1269-1282. (Pubitemid 47079354)
98. Vilas-Zornoza A, Agirre X, Martin-Palanco V et al. Frequent and simultaneous epigenetic inactivation of TP53 pathway genes in acute lymphoblastic leukemia. PloS One 2011; 6: e17012.
99. Bhatla T, Wang J, Morrison DJ, et al. Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia. Blood 2012; 119: 5201-5210.
100. Yanez L, Bermudez A, Richard C, et al. Successful induction therapy with decitabine in refractory childhood acute lymphoblastic leukemia. Leukemia 2009; 23: 1342-1343.
101. Paulson K, Kumar R, Ahsanuddin A, et al. Azacytidine as a novel agent in the treatment of acute lymphoblastic leukemia. Leuk Lymphoma 2011; 52: 134-136.
102. Garcia-Manero G, Thomas DA, Rytting ME, et al. Final report of a phase I trial of decitabine with or without HyperCVAD in relapsed acute lymphocytic leukemia (ALL).Blood 2010; 116(Suppl. 1): Abstract 867.
103. Webb MS, Harasym TO, Masin D, et al. Sphingomyelin- cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models. Br J Cancer 1995;72:896-904.
104. O'Brien S, Schiller G, Lister J, et al. High-dose vincristine sulfate liposome injection for advanced, relapsed and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol 2013; 31: 676-683.