The one-two punch: Combination treatment in chronic myeloid leukemia

Critical Reviews in Oncology/Hematology

Volumn 88, Issue 3, 2013, Pages 667-679

  Sweet, Kendra L ^a   Hazlehurst, Lori A ^a   Pinilla Ibarz, Javier ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

Author keywords

Chronic myeloid leukemia; Dasatinib; Imatinib; Leukemic stem cells; Nilotinib; Tyrosine kinase

Indexed keywords

4 (4 AMINO 5 (7 METHOXY 1H INDOL 2 YL)IMIDAZO[5,1 F][1,2,4]TRIAZIN 7 YL)CYCLOHEXANECARBOXYLIC ACID; 5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; ALPHA INTERFERON; BCR ABL PROTEIN; BMS 833923; CC 223; CWP 232291; DASATINIB; FEDRATINIB; GANDOTINIB; HEAT SHOCK PROTEIN 90 INHIBITOR; HISTONE DEACETYLASE 1; ISIS 481464; JANUS KINASE; LESTAURTINIB; LIPOXYGENASE INHIBITOR; MAMMALIAN TARGET OF RAPAMYCIN; MOMELOTINIB; NILOTINIB; NS 018; OPB 51602; PACRITINIB; PF 04449913; PHOSPHOPROTEIN PHOSPHATASE 2A; PRI 724; PYRIMETHAMINE; RUXOLITINIB; SARIDEGIB; SONIC HEDGEHOG PROTEIN; SONIDEGIB; STAT3 PROTEIN; STAT5 PROTEIN; UNCLASSIFIED DRUG; VISMODEGIB;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; B CELL LYMPHOMA; BONE MARROW; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC MYELOID LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; DOWNSTREAM PROCESSING; ENZYME ACTIVATION; ENZYME INHIBITION; ESSENSTIAL FIBROSIS; ESSENTIAL THROMBOCYTHEMIA MYELOFIBROSIS; EXTRACELLULAR MATRIX; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; LARGE CELL LYMPHOMA; LYMPHOMA; MANTLE CELL LYMPHOMA; MOLECULARLY TARGETED THERAPY; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROME; MYELOFIBROSIS; MYELOID METAPLASIA; PERIPHERAL T CELL LYMPHOMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PLASMACYTOMA; POLYCYTHEMIA VERA; POLYCYTHEMIA VERA MYELOFIBROSIS; POSTESSENTIAL THROMBOCYTHEMIA MYELOFIBROSIS; POSTPOLYCYTHEMIA VERA MYELOFIBROSIS; REVIEW; SIGNAL TRANSDUCTION; SMALL LYMPHOCYTIC LEUKEMIA; SOLID TUMOR; TUMOR MICROENVIRONMENT;

CHRONIC MYELOID LEUKEMIA; DASATINIB; IMATINIB; LEUKEMIC STEM CELLS; NILOTINIB; TYROSINE KINASE;

ANIMALS; ANTINEOPLASTIC AGENTS; BETA CATENIN; HEDGEHOG PROTEINS; HUMANS; JANUS KINASES; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; NEOPLASTIC STEM CELLS; PROTEIN KINASE INHIBITORS; PROTEIN PHOSPHATASE 2; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; TOR SERINE-THREONINE KINASES; WNT PROTEINS;

EID: 84888301272     PISSN: 10408428     EISSN: 18790461     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2013.07.017     Document Type: Review

References (100)

1. Heisterkamp N., Stam K., Groffen J., de Klein A., Grosveld G. Structural organization of the bcr gene and its role in the Ph' translocation. Nature 1985, 315(6022):758-761.
2. Nowell P.C., Hungerford D.A. Chromosome studies on normal and leukemic human leukocytes. Journal of the National Cancer Institute 1960, 25:85-109.
3. Rowley J.D. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973, 243(5405):290-293.
4. Deininger M.W., Goldman J.M., Melo J.V. The molecular biology of chronic myeloid leukemia. Blood 2000, 96(10):3343-3356.
5. O'Brien S.G., Guilhot F., Larson R.A., Gathmann I., Baccarani M., Cervantes F., et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. New England Journal of Medicine 2003, 348(11):994-1004.
6. Deininger M., O'Brien S.G., Guilhot F., Goldman J.M., Hochhaus A., Hughes T.P., 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 (ASH Annual Meeting Abstracts) 2009, 114(22):1126.
7. Mahon F.X., Rea D., Guilhot J., Guilhot F., Huguet F., Nicolini F., et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncology 2010, 11(11):1029-1035.
8. Mahon F.-X., Rea D., Guilhot J., Guilhot F., Huguet F., Nicolini F.E., et al. Discontinuation of imatinib in patients with chronic myeloid leukemia who have maintained complete molecular response: update results of the STIM study. Blood (ASH Annual Meeting Abstracts) 2011, 118(21):603.
9. Ross D.M., Branford S., Seymour J.F., Schwarer A.P., Arthur C., Bartley P.A., et al. Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia 2010, 24(10):1719-1724.
10. Chu S., McDonald T., Lin A., Chakraborty S., Huang Q., Snyder D.S., et al. Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment. Blood 2011, 118(20):5565-5572.
11. Saglio G., Kim D.W., Issaragrisil S., le Coutre P., Etienne G., Lobo C., et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. New England Journal of Medicine 2010, 362(24):2251-2259.
12. Kantarjian H., Shah N.P., Hochhaus A., Cortes J., Shah S., Ayala M., et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. New England Journal of Medicine 2010, 362(24):2260-2270.
13. Hochhaus A., Shah N.P., Cortes J.E., Baccarani M., Bradley-Garelik M.B., Dejardin D., et al. Dasatinib versus imatinib (IM) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): DASISION 3-year follow-up. Journal of Clinical Oncology 2012, 30(suppl):6504.
14. Kantarjian H.M., Kim D.-W., Issaragrisil S., Clark R.E., Reiffers J., Nicolini F.E., 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 (ASH Annual Meeting Abstracts) 2012, 120(21):1676.
15. Nair R.R., Tolentino J., Hazlehurst L.A. The bone marrow microenvironment as a sanctuary for minimal residual disease in CML. Biochemical Pharmacology 2010, 80(5):602-612.
16. Copland M., Hamilton A., Elrick L.J., Baird J.W., Allan E.K., Jordanides N., et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 2006, 107(11):4532-4539.
17. Corbin A.S., Agarwal A., Loriaux M., Cortes J., Deininger M.W., Druker B.J. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. Journal of Clinical Investigation 2011, 121(1):396-409.
18. Graham S.M., Jorgensen H.G., Allan E., Pearson C., Alcorn M.J., Richmond L., et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 2002, 99(1):319-325.
19. Konig H., Holtz M., Modi H., Manley P., Holyoake T.L., Forman S.J., et al. Enhanced BCR-ABL kinase inhibition does not result in increased inhibition of downstream signaling pathways or increased growth suppression in CML progenitors. Leukemia 2008, 22(4):748-755.
20. Konig H., Holyoake T.L., Bhatia R. Effective and selective inhibition of chronic myeloid leukemia primitive hematopoietic progenitors by the dual Src/Abl kinase inhibitor SKI-606. Blood 2008, 111(4):2329-2338.
21. Rawlings J.S., Rosler K.M., Harrison D.A. The JAK/STAT signaling pathway. Journal of Cell Science 2004, 117(Pt 8):1281-1283.
22. Levine R.L., Pardanani A., Tefferi A., Gilliland D.G. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nature Reviews Cancer 2007, 7(9):673-683.
23. Samanta A., Perazzona B., Chakraborty S., Sun X., Modi H., Bhatia R., et al. Janus kinase 2 regulates BCR-ABL signaling in chronic myeloid leukemia. Leukemia 2011, 25(3):463-472.
24. Bewry N.N., Nair R.R., Emmons M.F., Boulware D., Pinilla-Ibarz J., Hazlehurst L.A. Stat3 contributes to resistance toward BCR-ABL inhibitors in a bone marrow microenvironment model of drug resistance. Mol Cancer Ther. 2008, 7(10):3169-3175.
25. Turhan A.G. STAT5 as a CML target: STATinib therapies?. Blood 2011, 117(12):3252-3253.
26. Carlesso N., Frank D.A., Griffin J.D. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by BCR/ABL. Journal of Experimental Medicine 1996, 183(3):811-820.
27. Warsch W., Kollmann K., Eckelhart E., Fajmann S., Cerny-Reiterer S., Holbl A., et al. High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia. Blood 2011, 117(12):3409-3420.
28. Verstovsek S. Study to Assess the Safety of Azd1480 in Patients with Myeloproliferative Diseases 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT00910728.
29. Silverman L., Hoffman R. CEP-701 (Lestaurtinib) in Myelofibrosis 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT00668421?term=Lestaurtinib%38rank=1.
30. Santos F.P., Kantarjian H.M., Jain N., Manshouri T., Thomas D.A., Garcia-Manero G., et al. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood 2010, 115(6):1131-1136.
31. Levis M., Ravandi F., Wang E.S., Baer M.R., Perl A., Coutre S., 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(12):3294-3301.
32. Brown P. Combination Chemotherapy With or Without Lestaurtinib in Treating Infants With Newly Diagnosed Acute Lymphoblastic Leukemia 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT00557193?term=NCT00557193%38rank=1.
33. Sterling K. Safety Study Evaluating Twice-Daily Administration of Cyt387 in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT01423058?term=CYT387%38rank=2.
34. Tefferi A. Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-Polycythemia Vera (PV) or Post-Essential Thrombocythemia (ET) 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT00935987?term=CYT387%38rank=1.
35. Eli Lilly and Company A Phase 1 Study of LY2784544 in Patients With Jak2 V617F-Positive Myeloproliferative Disorders 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01134120?term=NCT01134120%38rank=1.
36. Eli Lilly and Company A Phase 2 Study of LY278544 in Patients With Myeloproliferative Neoplasms 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01594723?term=NCT01594723%38rank=1.
37. Verstovsek S. A Phase 1/2, Open-Label, Dose-Escalation Multi-Center Study to Assess the Safety, Tolerability, PK and PD of Orally Administered NS-018 in Patients With Primary Myelofibrosis (MF), Post-Polycythemia Vera MF, or Post-Essential Thrombocythemia MF 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01423851?term=NCT01423851%38rank=1.
38. Jakafi Jakafi (Ruxolitinib) Prescribing Information 2011, Incyte Corporation, Wilmington, DE.
39. Talpaz M., Hamburg S.L., Jamieson K. Preliminary safety and efficacy of ruxolitinib in patients with primary and secondary myelofibrosis with platelet counts of 50-100(10(9) (abstract 6630). Paper Presented At: Annual Meeting of the American Society of Clinical Oncology 2012.
40. Verstovsek S., Kantarjian H., Mesa R.A., Pardanani A.D., Cortes-Franco J., Thomas D.A., et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. New England Journal of Medicine 2010, 363(12):1117-1127.
41. Novartis Pharmaceuticals A Multi-National Open-Label Phase II Study of the JAK Inhibitor INC424 in Patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01392443?term=NCT01392443%38rank=1.
42. Verstovsek S. Evaluation of Ruxolitinib and Lenalidomide Combination as a Therapy for Patients with Myelofibrosis 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01375140?term=NCT01375140%38rank=1.
43. Verstovsek S. A Phase I/II Study to Determine the Safety and Efficacy of Ruxolitinib, a JAK1/JAK2 Inhibitor, in Subjects with Relapsed or Refractory Acute Leukemia 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01251965?term=NCT01251965%38rank=1.
44. Ravandi-Kashani F. INCB018424 in Patients with Advanced Hematologic Malignancies 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT00674479?term=ruxolitinib%38rank=18.
45. Eghtedar A., Verstovsek S., Estrov Z., Burger J., Cortes J., Bivins C., et al. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood 2012, 119(20):4614-4618.
46. Vose J.M. A Phase 2 Multicenter, Investigator Initiated Study of Oral Ruxolitinib Phosphate for the Treatment of Relapsed or Refractory Diffuse Large B-Cell and Peripheral T-Cell Non-Hodgkin Lymphoma 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01431209?term=NCT01431209%38rank=1.
47. Sanofi-Aventis Study with SAR302503 in Patients with Polycythemia Vera or Essential Thrombocythemia 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT00079482?term=Lestaurtinib%38rank=3.
48. Garcia-Manero G. Phase II Study of SB1518 for Patients with Myelodysplastic Syndrome (MDS) 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01436084?term=NCT01436084%38rank=1.
49. Verstovsek S. A Phase 1/2 Study of SB1518 for the Treatment of Advanced Myeloid Malignancies 2012, (accessed 18.09.12). http://clinicaltrials.gov/ct2/show/NCT00719836?term=NCT00719836%38rank=1.
50. Deeg H.J., Odenike O., Scott B.L., Estrov Z., Cortes J.E., Thomas D.A., et al. Phase II study of SB1518, an orally available novel JAK2 inhibitor, in patients with myelofibrosis. Journal of Clinical Oncology 2011, 29(5):6515.
51. Komrokji R.S., Wadleigh M., Seymour J.F., Roberts A.W., To L.B., Zhu H.J., et al. Results of a phase 2 study of pacritinib (SB1518), a novel oral JAK2 inhibitor, in patients with primary, post-polycythemia vera, and post-essential thrombocythemia myelofibrosis. Blood (ASH Annual Meeting Abstracts) 2011, 118(21):282.
52. Younes A. A Phase 1 Study of SB1518 for the Treatment of Advanced Lymphoid Malignancies 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT00741871?term=NCT00741871%38rank=1.
53. Younes A. A Phase 2 Safety and Efficacy Study of SB1518 for the Treatment of Advanced Lymphoid Malignancies 2012.
54. Isis Pharmaceuticals Phase I, Open-Label, Dose-Escalation Study of ISIS-STAT3Rx, Administered to Patients with Advanced Cancers 2012, (accessed 18.07.12). http://www.clinicalconnection.com/exp/EPVS.aspx?studyID=322467%38slID=5291032.
55. Otsuka Pharmaceutical A Dose-Escalation Trial to Investigate the Safety and Tolerability of OPB-51602 in Patients with Relapsed or Refractory Hematologic Malignancies (Phase 1) 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01344876?term=NCT01344876%38rank=1.
56. Brown J.R. Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT01066663.
57. Bristol-Myers-Squibb Multiple Ascending Dose (MAD) Combination in Subjects with Multiple Myeloma 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT00884546?term=BMS-833923+AND+myeloma%38rank=1.
58. Bristol-Myers-Squibb Dasatinib (BMS-354825) Combined with SMO Inhibitor (BMS-833923; XL139) in CML with Resistance or Suboptimal Response to a Prior TKI 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01218477?term=NCT01218477%38rank=1.
59. Huff C.A. GDC-0449 in Treating Patients with High-risk First Remission or Relapsed Multiple Myeloma Who Received An Autologous Stem Cell Transplant 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT01330173.
60. Verstovsek S. A Phase 2 Study With IPI-926 in Patients With Myelofibrosis 2012, (accessed 18.09.12). http://clinicaltrials.gov/ct2/show/NCT01371617?term=NCT+01371617%38rank=1.
61. Novartis Pharmaceuticals A Single-Arm Dose-Finding Phase IB Multicenter Study of the Oral Smoothened Antagonist LDE225 in Combination With Nilotinib in Chronic Phase Chronic Myeloid Leukemia Patients Who Have Failed Prior Therapy With Other BCR-ABL Tyrosine-Kinase Inhibitors 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01456676?term=NCT01456676%38rank=1.
62. Pfizer Inc A Study of PF-04449913 in Select Hematologic Malignancies 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT00953758.
63. Pfizer Inc A Phase 1B Study to Evaluate the Safety and Preliminary Efficacy of PF-04449913, An Oral Hedgehog Inhibitor, in Combination With Intensive Chemotherapy, Low Dose Ara-C or Decitabine in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01546038?term=NCT01546038%38rank=1.
64. de Haan H. Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients 2012, (accessed 18.07.12). http://clinicaltrials.gov/ct2/show/NCT01398462.
65. Cortes J. An Open-Label, Dose-Escalation Phase I/II Study of PRI-724 for Patients with Advanced Myeloid Malignancies 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01606579?term=NCT01606579%38rank=1.
66. Hege K. Phase 1/2, Multi-Center, Open-Label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the mTOR Knase Inhibitor CC-223 Administered Orally to Subjects with Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma 2012, (accessed 02.08.12). http://www.clinicaltrials.gov/ct2/show/NCT01177397?term=NCT01177397%38rank=1.
67. Astellas Pharma Inc A Phase 1 Dose-escalation Study of Intermittent, Once Weekly, and Continuous Daily Oral OSI-027 Dosing in Patients with Advanced Solid Tumors or Lymphoma 2012.
68. Nair R.R., Tolentino J.H., Argilagos R.F., Zhang L., Pinilla-Ibarz J., Hazlehurst L.A. Potentiation of Nilotinib-mediated cell death in the context of the bone marrow microenvironment requires a promiscuous JAK inhibitor in CML. Leukemia Research 2012, 36(6):756-763.
69. Nelson E.A., Walker S.R., Weisberg E., Bar-Natan M., Barrett R., Gashin L.B., et al. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood 2011, 117(12):3421-3429.
70. Nam S., Scuto A., Yang F., Chen W., Park S., Yoo H.S., et al. Indirubin derivatives induce apoptosis of chronic myelogenous leukemia cells involving inhibition of Stat5 signaling. Molecular Oncology 2012, 6(3):276-283.
71. Mar B.G., Amakye D., Aifantis I., Buonamici S. The controversial role of the Hedgehog pathway in normal and malignant hematopoiesis. Leukemia 2011, 25(11):1665-1673.
72. Gupta S., Takebe N., Lorusso P. Targeting the Hedgehog pathway in cancer. Therapeutic Advances in Medical Oncology 2010, 2(4):237-250.
73. Dierks C., Beigi R., Guo G.R., Zirlik K., Stegert M.R., Manley P., et al. Expansion of BCR-ABL-positive leukemic stem cells is dependent on Hedgehog pathway activation. Cancer Cell 2008, 14(3):238-249.
74. Zhao C., Chen A., Jamieson C.H., Fereshteh M., Abrahamsson A., Blum J., et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 2009, 458(7239):776-779.
75. Lie D.C., Colamarino S.A., Song H.J., Desire L., Mira H., Consiglio A., et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature 2005, 437(7063):1370-1375.
76. Trowbridge J.J., Moon R.T., Bhatia M. Hematopoietic stem cell biology: too much of a Wnt thing. Nature Immunology 2006, 7(10):1021-1023.
77. Jamieson C.H., Ailles L.E., Dylla S.J., Muijtjens M., Jones C., Zehnder J.L., et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. New England Journal of Medicine 2004, 351(7):657-667.
78. Heidel F.H., Bullinger L., Feng Z., Wang Z., Neff T.A., Stein L., et al. Genetic and pharmacologic inhibition of beta-catenin targets imatinib-resistant leukemia stem cells in CML. Cell Stem Cell 2012, 10(4):412-424.
79. Gregory M.A., Phang T.L., Neviani P., Alvarez-Calderon F., Eide C.A., O'Hare T., et al. Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of BCR-ABL. Cancer Cell 2010, 18(1):74-87.
80. Arroyo J.D., Hahn W.C. Involvement of PP2A in viral and cellular transformation. Oncogene 2005, 24(52):7746-7755.
81. Switzer C.H., Cheng R.Y., Vitek T.M., Christensen D.J., Wink D.A., Vitek M.P. Targeting SET/I(2)PP2A oncoprotein functions as a multi-pathway strategy for cancer therapy. Oncogene 2011, 30(22):2504-2513.
82. Perrotti D., Jamieson C., Goldman J., Skorski T. Chronic myeloid leukemia: mechanisms of blastic transformation. Journal of Clinical Investigation 2010, 120(7):2254-2264.
83. Neviani P., Santhanam R., Trotta R., Notari M., Blaser B.W., Liu S., 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(5):355-368.
84. Teachey D.T., Grupp S.A., Brown V.I. Mammalian target of rapamycin inhibitors and their potential role in therapy in leukaemia and other haematological malignancies. British Journal of Haematology 2009, 145(5):569-580.
85. Foster K.G., Fingar D.C. Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. Journal of Biological Chemistry 2010, 285(19):14071-14077.
86. Carayol N., Vakana E., Sassano A., Kaur S., Goussetis D.J., Glaser H., et al. Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells. Proceedings of the National Academy of Sciences of the United States of America 2010, 107(28):12469-12474.
87. Yee K.W., Zeng Z., Konopleva M., Verstovsek S., Ravandi F., Ferrajoli A., et al. Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies. Clinical Cancer Research 2006, 12(17):5165-5173.
88. Janes M.R., Limon J.J., So L., Chen J., Lim R.J., Chavez M.A., et al. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nature Medicine 2010, 16(2):205-213.
89. Rousselot P., Huguet F., Rea D., Legros L., Cayuela J.M., Maarek O., et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 2007, 109(1):58-60.
90. Rousselot P., Makhoul P.C., Rea D., Agape P., Nicolini F.E., Legros L., et al. Fluctuating values of molecular residual disease (MRD) without molecular progression after imatinib discontinuation in patients (pts) with chronic myeloid leukemia (CML) who have maintained complete molecular response: implications for re-treatment criteria and role of prior interferon therapy. A pilot study of the French CML Group (FILMC). Blood (ASH Annual Meeting Abstracts) 2011, 118(21):3781.
91. Essers M.A., Offner S., Blanco-Bose W.E., Waibler Z., Kalinke U., Duchosal M.A., et al. IFNalpha activates dormant haematopoietic stem cells in vivo. Nature 2009, 458(7240):904-908.
92. Hehlmann R., Lauseker M., Jung-Munkwitz S., Leitner A., Muller M.C., Pletsch N., et al. Tolerability-adapted imatinib 800mg/d versus 400mg/d versus 400mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. Journal of Clinical Oncology 2011, 29(12):1634-1642.
93. Palandri F., Castagnetti F., Iacobucci I., Martinelli G., Amabile M., Gugliotta G., et al. The response to imatinib and interferon-alpha 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 2010, 95(8):1415-1419.
94. Preudhomme C., Guilhot J., Nicolini F.E., Guerci-Bresler A., Rigal-Huguet F., Maloisel F., et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. New England Journal of Medicine 2010, 363(26):2511-2521.
95. Simonsson B., Gedde-Dahl T., Markevarn B., Remes K., Stentoft J., Almqvist A., et al. Combination of pegylated IFN-alpha2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood 2011, 118(12):3228-3235.
96. Burgess A., Ruefli A., Beamish H., Warrener R., Saunders N., Johnstone R., et al. Histone deacetylase inhibitors specifically kill nonproliferating tumour cells. Oncogene 2004, 23(40):6693-6701.
97. Minucci S., Pelicci P.G. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nature Reviews Cancer 2006, 6(1):38-51.
98. Zhang B., Strauss A.C., Chu S., Li M., Ho Y., Shiang K.D., et al. Effective targeting of quiescent chronic myelogenous leukemia stem cells by histone deacetylase inhibitors in combination with imatinib mesylate. Cancer Cell 2010, 17(5):427-442.
99. Chen Y., Li D., Li S. The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia. Cell Cycle 2009, 8(21):3488-3492.
100. Den R.B., Lu B. Heat shock protein 90 inhibition: rationale and clinical potential. Therapeutic Advances in Medical Oncology 2012, 4(4):211-218.