Bcl-xL anti-apoptotic network is dispensable for development and maintenance of CML but is required for disease progression where it represents a new therapeutic target

Leukemia

Volumn 27, Issue 10, 2013, Pages 1996-2005

  Harb, J G ^a,b   Neviani, P ^a,c   Chyla, B J ^b   Ellis, J J ^a   Ferenchak, G J ^a   Oaks, J J ^a   Walker, C J ^a   Hokland, P ^d   Roy, D C ^e   Caligiuri, M A ^a,c,f   Marcucci, G ^a,c,f   Huettner, C S ^b,g   Perrotti, D ^a,c  

^a Human Cancer Genetics Program   (United States)

^b BLOOD RESEARCH INSTITUTE   (United States)

^c OHIO STATE UNIVERSITY   (United States)

^d AARHUS UNIVERSITY HOSPITAL   (Denmark)

^e MAISONNEUVE ROSEMONT HOSPITAL   (Canada)

^f Department of Internal Medicine ^*  (United States)

^g HARVARD MEDICAL SCHOOL   (United States)

Author keywords

ABT 263; ABT 737; Bcl xL; CML blast crisis; PP242

Indexed keywords

2 (4 AMINO 1 ISOPROPYL 1H PYRAZOLO[3,4 D]PYRIMIDIN 3 YL) 1H INDOL 5 OL; 2 MORPHOLINO 8 PHENYLCHROMONE; BCR ABL PROTEIN; IMATINIB; NAVITOCLAX; PROTEIN BAD; PROTEIN BCL X; PROTEIN BCL XL; RAPAMYCIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BONE MARROW CELL; BONE MARROW STROMAL CELL; CD34 SELECTION; CELL SURVIVAL; CHRONIC MYELOID LEUKEMIA; CONTROLLED STUDY; GENE DELETION; GENE EXPRESSION; HEMATOPOIETIC STEM CELL; HUMAN; HUMAN CELL; LEUKEMIA CELL; LEUKEMIA CELL LINE; MOUSE; MYELOPROLIFERATIVE DISORDER; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STEM CELL; STROMA CELL; TUMOR GROWTH; TUMOR XENOGRAFT;

ANILINE COMPOUNDS; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BCL-X PROTEIN; BLAST CRISIS; DISEASE PROGRESSION; FEMALE; FLOW CYTOMETRY; FUSION PROTEINS, BCR-ABL; HUMANS; INDOLES; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; MALE; MICE; MICE, TRANSGENIC; PURINES; STEM CELLS; SULFONAMIDES;

EID: 84885591977     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2013.151     Document Type: Article

References (60)

1. Cortes J, Kantarjian H. How I treat newly diagnosed chronic phase CML. Blood 2012; 120: 1390-1397.
2. Hehlmann R. How I treat CML blast crisis. Blood 2012; 120: 737-747.
3. Hochhaus A, O'Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia (vol 23, pg 1054, 2009). Leukemia 2010; 24: 1102-1102.
4. Perrotti D, Jamieson C, Goldman J, Skorski T. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest 2010; 120: 2254-2264.
5. Quintas-Cardama A, Cortes J. Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood 2009; 113: 1619-1630.
6. Milojkovic D, Apperley JF, Gerrard G, Ibrahim AR, Szydlo R, Bua M et al. Responses to second-line tyrosine kinase inhibitors are durable: an intention-to-treat analysis in chronic myeloid leukemia patients. Blood 2012; 119: 1838-1843.
7. Karvela M, Helgason GV, Holyoake TL. Mechanisms and novel approaches in overriding tyrosine kinase inhibitor resistance in chronic myeloid leukemia. Expert Rev Anticancer Ther 2012; 12: 381-392.
8. Hantschel O, Rix U, Superti-Furga G. Target spectrum of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib. Leuk Lymphoma 2008; 49: 615-619.
9. Bewry NN, Nair RR, Emmons MF, Boulware D, Pinilla-Ibarz J, Hazlehurst LA. Stat3 contributes to resistance toward BCR-ABL inhibitors in a bone marrow microenvironment model of drug resistance. Mol Cancer Ther 2008; 7: 3169-3175.
10. Traer E, MacKenzie R, Snead J, Agarwal A, Eiring AM, O'Hare T et al. Blockade of JAK2-mediated extrinsic survival signals restores sensitivity of CML cells to ABL inhibitors. Leukemia 2012; 26: 1140-1143.
11. Sanchez-Garcia I, Grutz G. Tumorigenic activity of the BCR-ABL oncogenes is mediated by BCL2. Proc Natl Acad Sci USA 1995; 92: 5287-5291.
12. Amarante-Mendes GP, McGahon AJ, Nishioka WK, Afar DEH, Witte ON, Green DR. Bcl-2-independent Bcr-Abl-mediated resistance to apoptosis: protection is correlated with up regulation of Bcl-x(L). Oncogene 1998; 16: 1383-1390.
13. Horita M, Andreu EJ, Benito A, Arbona C, Sanz C, Benet I et al. Blockade of the Bcr-Abl kinase activity induces apoptosis of chronic myelogenous leukemia cells by suppressing signal transducer and activator of transcription 5-dependent expression of Bcl-(XL). J Exp Med 2000; 191: 977-984.
14. Aichberger KJ, Mayerhofer M, Krauth MT, Skvara H, Florian S, Sonneck K et al. Identification of mcl-1 as a BCR/ABL-dependent target in chronic myeloid leukemia (CML): evidence for cooperative antileukemic effects of imatinib and mcl-1 antisense oligonucleotides. Blood 2005; 105: 3303-3311.
15. Soliera AR, Mariani SA, Audia A, Lidonnici MR, Addya S, Ferrari-Amorotti G et al. Gfi-1 inhibits proliferation and colony formation of p210BCR/ABL-expressing cells via transcriptional repression of STAT 5 and Mcl-1. Leukemia 2012; 26: 1555-1563.
16. Allan EK, Holyoake TL, Craig AR, Jorgensen HG. Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells. Leukemia 2011; 25: 985-994.
17. Chen Y, Hu Y, Michaels S, Segal D, Brown D, Li S. Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice. Leukemia 2009; 23: 1446-1454.
18. Gonzalez-Herrero I, Vicente-Duenas C, Orfao A, Flores T, Jimenez R, Cobaleda C et al. Bcl2 is not required for the development and maintenance of leukemia stem cells in mice. Carcinogenesis 2010; 31: 1292-1297.
19. Opferman JT, Iwasaki H, Ong CC, Suh H, Mizuno S, Akashi K et al. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 2005; 307: 1101-1104.
20. Kuroda J, Kimura S, Andreeff M, Ashihara E, Kamitsuji Y, Yokota A et al. ABT-737 is a useful component of combinatory chemotherapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms. Br J Haematol 2008; 140: 181-190.
21. High LM, Szymanska B, Wilczynska-Kalak U, Barber N, O'Brien R, Khaw SL et al. The Bcl-2 homology domain 3 mimetic ABT-737 targets the apoptotic machinery in acute lymphoblastic leukemia resulting in synergistic in vitro and in vivo interactions with established drugs. Mol Pharmacol 2010; 77: 483-494.
22. Harb JG, Chyla BI, Huettner CS. Loss of Bcl-x in Ph B-ALL increases cellular proliferation and does not inhibit leukemogenesis. Blood 2008; 111: 3760-3769.
23. Mak DH, Wang RY, Schober WD, Konopleva M, Cortes J, Kantarjian H et al. Activation of apoptosis signaling eliminates CD34() progenitor cells in blast crisis CML independent of response to tyrosine kinase inhibitors. Leukemia 2012; 26: 788-794.
24. Milojkovic D, Apperley J. Mechanisms of resistance to imatinib and second-generation tyrosine inhibitors in chronic myeloid leukemia. Clin Cancer Res 2009; 15: 7519-7527.
25. Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 2008; 68: 3421-3428.
26. Kuroda J, Puthalakath H, Cragg MS, Kelly PN, Bouillet P, Huang DCS et al. Bim and Bad mediate imatinib-induced killing of Bcr/Abl() leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc Natl Acad Sci USA 2006; 103: 14907-14912.
27. Salomoni P, Condorelli F, Sweeney SM, Calabretta B. Versatility of BCR/ABLexpressing leukemic cells in circumventing proapoptotic BAD effects. Blood 2000; 96: 676-684.
28. Neshat MS, Raitano AB, Wang HG, Reed JC, Sawyers CL. The survival function of the Bcr-Abl oncogene is mediated by Bad-dependent and-independent pathways: Roles for phosphatidylinositol 3-kinase and Raf. Mol Cell Biol 2000; 20: 1179-1186.
29. Danial NN. BAD: undertaker by night, candyman by day. Oncogene 2008; 27: S53-S70.
30. Ly C, Arechiga AF, Melo JV, Walsh CM, Ong ST. Bcr-Abl kinase modulates the translation regulators ribosomal protein S6 and 4E-BP1 in chronic myelogenous leukemia cells via the mammalian target of rapamycin. Cancer Res 2003; 63: 5716-5722.
31. Skorski T, Bellacosa A, NieborowskaSkorska M, Majewski M, Martinez R, Choi JK et al. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway. EMBO J 1997; 16: 6151-6161.
32. Bhagwat SV, Crew AP. Novel inhibitors of mTORC1 and mTORC2. Curr Opin Investig Drugs 2010; 11: 638-645.
33. Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. Plos Biol 2009; 7: 371-383.
34. Carayol N, Vakana E, Sassano A, Kaur S, Goussetis DJ, Glaser H et al. Critical roles for mTORC2-and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells. Proc Natl Acad Sci USA 2010; 107: 12469-12474.
35. Janes MR, Limon JJ, So L, Chen J, Lim RJ, Chavez MA et al. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat Med 2010; 16: 205-U115.
36. Koschmieder S, Gottgens B, Zhang P, Iwasaki-Arai J, Akashi K, Kutok JL et al. Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis. Blood 2005; 105: 324-334.
37. Iervolino A, Santilli G, Trotta R, Guerzoni C, Cesi V, Bergamaschi A et al. hnRNP A1 nucleocytoplasmic shuttling activity is required for normal myelopoiesis and BCR/ ABL leukemogenesis. Mol Cell Biol 2002; 22: 2255-2266.
38. Huettner CS, Zhang P, Van Etten RA, Tenen DG. Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nat Genet 2000; 24: 57-60.
39. Radomska HS, Gonzalez DA, Okuno Y, Iwasaki H, Nagy A, Akashi K et al. Transgenic targeting with regulatory elements of the human CD34 gene. Blood 2002; 100: 4410-4419.
40. Wagner KU, Claudio E, Rucker EB, Riedlinger G, Broussard C, Schwartzberg PL et al. Conditional deletion of the Bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly. Development 2000; 127: 4949-4958.
41. Mihara K, Imai C, Coustan-Smith E, Dome JS, Dominici M, Vanin E et al. Development and functional characterization of human bone marrow mesenchymal cells immortalized by enforced expression of telomerase. Br J Haematol 2003; 120: 846-849.
42. Berquin IM, Min Y, Wu R, Wu J, Perry D, Cline JM et al. Modulation of prostate cancer genetic risk by ornega-3 and ornega-6 fatty acids. J Clin Invest 2007; 117: 1866-1875.
43. Perrotti D, Cesi V, Trotta R, Guerzoni C, Santilli G, Campbell K et al. BCR-ABL suppresses C/EBP alpha expression through inhibitory action of hnRNP E2. Nat Genet 2002; 30: 48-58.
44. Notari M, Neviani P, Santhanam R, Blaser BW, Chang JS, Galietta A et al. A MAPK/ HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation. Blood 2006; 107: 2507-2516.
45. Chiang CW, Harris G, Ellig C, Masters SC, Subramanian R, Shenolikar S et al. Protein phosphatase 2A activates the proapoptotic function of BAD in interleukin-3-dependent lymphoid cells by a mechanism requiring 14-3-3 dissociation. Blood 2001; 97: 1289-1297.
46. Cirinna M, Trotta R, Salomoni P, Kossev P, Wasik M, Perrotti D et al. Bcl-2 expression restores the leukemogenic potential of a BCR/ABL mutant defective in transformation. Blood 2000; 96: 3915-3921.
47. Fang XJ, Yu SX, Eder A, Mao ML, Bast RC, Boyd D et al. Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway. Oncogene 1999; 18: 6635-6640.
48. Copland M, Hamilton A, Elrick LJ, Baird JW, Allan EK, 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: 4532-4539.
49. Jamieson CHM, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 2004; 351: 657-667.
50. Eiring AM, Neviani P, Santhanam R, Oaks JJ, Chang JS, Notari M 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.
51. Calabretta B, Perrotti D. The biology of CML blast crisis. Blood 2004; 103: 4010-4022.
52. Jaiswal S, Traver D, Miyamoto T, Akashi K, Lagasse E, Weissman IL. Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. Proc Natl Acad Sci USA 2003; 100: 10002-10007.
53. Ravandi FM, Kantarjian HM, Talpaz M, O'Brien S, Faderl S, Giles FJ et al. Expression of apoptosis proteins in chronic myelogenous leukemia. Cancer 2001; 91: 9.
54. Evangelisti C, Ricci F, Tazzari P, Tabellini G, Battistelli M, Falcieri E et al. Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia. Leukemia 2011; 25: 781-791.
55. Spender LC, Inman GJ. Phosphoinositide 3-kinase/AKT/mTORC1/2 Signaling Determines Sensitivity of Burkitt's Lymphoma Cells to BH3 mimetics. Mol Cancer Res 2012; 10: 347-359.
56. Airiau K, Mahon F-X, Josselin M, Jeanneteau M, Turcq B, Belloc F. ABT-737 increases tyrosine kinase inhibitor-induced apoptosis in chronic myeloid leukemia cells through XIAP downregulation and sensitizes CD34() CD38(-) population to imatinib. Exp Hematol 2012; 40: 367-378.
57. Merino D, Khaw SL, Glaser SP, Anderson DJ, Belmont LD, Wong C et al. Bcl-2, Bclx( L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells. Blood 2012; 119: 5807-5816.
58. Zeng Z, Shi YX, Tsao T, Qiu Y, Kornblau SM, Baggerly KA et al. Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment. Blood 2012; 120: 2679-2689.
59. Konopleva M, Contractor R, Tsao T, Samudio I, Ruvalo PP, Kitada S et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 2006; 10: 375-388.
60. van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 2006; 10: 389-399.