Dokument

Zusammenfassung:
Resistenz gegenüber IM stellt ein klinisches relevantes und in den zugrunde liegenden Mechanismen bislang nur teilweise verstandenes Problem dar. Um mögliche Ursachen für eine Resistenzentwicklung zu finden, bedienten wir uns eines shRNA basierten Screen mit der von Brummelkamp et al. 2002 etablierten NKI-Library. K562-wt wurden mit der Library und Kontroll-Vektoren transfiziert und mit 750 nM IM drei Wochen inkubiert. Es konnten insgesamt vier Gene isoliert werden: Tanscriptional regulating factor 1 (TRERF1), ein Transkriptionsfaktor, der primär im Zusammenhang mit Steroidhormonsynthese und Tamoxifenresistenz bei Mamm- akarzinom beschrieben ist. BCL2-like Protein 11 (Bim, Bcl-2 interacting mediator of cell death), ein Protein der Bcl-2 Familie, welches Apoptose regelt und als Resistenzmechanismus gegenüber IM beschrieben ist. Seizure-Related 6 Homolog (Mouse)-Like 2 (SEZ6L2) ist ein Oberflächenprotein, dessen Gen auf dem Chromosom 16p11.2 lokalisiert ist und von welchem angenommen wird, dass es Kandidatengene für Erkrankungen des autistischen Formenkreises (autism spectrum disorders [ASD]) beinhaltet. Homo sapiens Enhancer of Zeste Homolog 1 (Drosophila) (EZH1) ist ein Gen der Polycomp Gruppe (PcG). Proteine dieser Gruppe sind an der epigenetischen Regulation in der Embryonalentwicklung durch Methylierung des Histon H3 am Lysin-Rest 27 (H3K27) beteiligt.

Bibliographie / References

1. T. Skorski, M. Nieborowska-Skorska, C. Szczylik, P. Kanakaraj, D. Perrotti, G. Zon, A. Gewirtz, B. Perussia, and B. Calabretta. C-raf-1 serine/threonine kinase is required in bcr/abl-dependent and normal hematopoiesis. Cancer Res, 55(11):2275–2278, Jun 1995.
2. P. le Coutre, E. Tassi, M. Varella-Garcia, R. Barni, L. Mologni, G. Cabrita, E. Mar- chesi, R. Supino, and C. Gambacorti-Passerini. Induction of resistance to the abel- son inhibitor sti571 in human leukemic cells through gene amplification. Blood, 95(5):1758–1766, Mar 2000.
3. Anastasia Khvorova, Angela Reynolds, and Sumedha D Jayasena. Functional sirnas and mirnas exhibit strand bias. Cell, 115(2):209–216, Oct 2003.
4. B. J. Druker, S. Tamura, E. Buchdunger, S. Ohno, G. M. Segal, S. Fanning, J. Zimmermann, and N. B. Lydon. Effects of a selective inhibitor of the abl tyrosine kinase on the growth of bcr-abl positive cells. Nat Med, 2(5):561–566, May 1996.
5. Zamore. A cellular function for the rna-interference enzyme dicer in the maturation of the let-7 small temporal rna. Science, 293(5531):834–838, Aug 2001.
6. Katrien Berns, E. Marielle Hijmans, Jasper Mullenders, Thijn R Brummelkamp, Arno Velds, Mike Heimerikx, Ron M Kerkhoven, Mandy Madiredjo, Wouter Nij- kamp, Britta Weigelt, Reuven Agami, Wei Ge, Guy Cavet, Peter S Linsley, Rode- rick L Beijersbergen, and René Bernards. A large-scale rnai screen in human cells identifies new components of the p53 pathway. Nature, 428(6981):431–437, Mar 2004.
7. René Bernards, Thijn R Brummelkamp, and Roderick L Beijersbergen. shrna libraries and their use in cancer genetics. Nat Methods, 3(9):701–706, Sep 2006.
8. Hagop M Kantarjian, Susan O'Brien, Jorge E Cortes, Jianqin Shan, Francis J Giles, Mary Beth Rios, Stefan H Faderl, William G Wierda, Alessandra Ferrajoli, Srdan Verstovsek, Michael J Keating, Emil J Freireich, and Moshe Talpaz. Complete cytogenetic and molecular responses to interferon-alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer, 97(4):1033–1041, Feb 2003.
9. Geraldo Barroso Cavalcanti, Flavia da Cunha Vasconcelos, Giselle Pinto de Faria, Marcos Antônio Maurício Scheiner, Jane de Almeida Dobbin, Claudete Esteves Klumb, and Raquel C Maia. Coexpression of p53 protein and mdr functional phenotype in leukemias: the predominant association in chronic myeloid leukemia. Cytometry B Clin Cytom, 61(1):1–8, Sep 2004.
10. Saurabh Singh, Ajit S Narang, and Ram I Mahato. Subcellular fate and off-target effects of sirna, shrna, and mirna. Pharm Res, Oct 2011.
11. Aimee L Jackson and Peter S Linsley. Recognizing and avoiding sirna off-target effects for target identification and therapeutic application. Nat Rev Drug Discov, 9(1):57–67, Jan 2010.
12. Ian J MacRae, Kaihong Zhou, and Jennifer A Doudna. Structural determinants of rna recognition and cleavage by dicer. Nat Struct Mol Biol, 14(10):934–940, Oct 2007.
13. D. G. Savage, R. M. Szydlo, and J. M. Goldman. Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period. Br J Haematol, 96(1):111–116, Jan 1997.
14. T. Jonuleit, C. Peschel, R. Schwab, H. van der Kuip, E. Buchdunger, T. Fischer, C. Huber, and W. E. Aulitzky. Bcr-abl kinase promotes cell cycle entry of primary myeloid cml cells in the absence of growth factors. Br J Haematol, 100(2):295– 303, Feb 1998.
15. John W Pham and Erik J Sontheimer. Molecular requirements for rna-induced silencing complex assembly in the drosophila rna interference pathway. J Biol Chem, 280(47):39278–39283, Nov 2005.
16. Andreas Burchert and Andreas Neubauer. Interferon alpha and t-cell responses in chronic myeloid leukemia. Leuk Lymphoma, 46(2):167–175, Feb 2005.
17. Ashu Kumari, Cornelia Brendel, Andreas Hochhaus, Andreas Neubauer, and Andre- as Burchert. Low bcr-abl expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib. Blood, 119(2):530–539, Jan 2012.
18. R¸diger Hehlmann. How i treat cml blast crisis. Blood, 120(4):737–747, Jul 2012.
19. Lovorka Stojic, Zuzana Jasencakova, Carolina Prezioso, Alexandra St¸tzer, Bea- trice Bodega, Diego Pasini, Rebecca Klingberg, Chiara Mozzetta, Raphael Mar- gueron, Pier Lorenzo Puri, Dirk Schwarzer, Kristian Helin, Wolfgang Fischle, and Valerio Orlando. Chromatin regulated interchange between polycomb repressive complex 2 (prc2)-ezh2 and prc2-ezh1 complexes controls myogenin activation in skeletal muscle cells. Epigenetics Chromatin, 4:16, 2011.
20. François Guilhot, Brian Druker, Richard A Larson, Insa Gathmann, Charlene So, Roger Waltzman, and Stephen G O'Brien. High rates of durable response are achieved with imatinib after treatment with interferon alpha plus cytarabine: re- sults from the international randomized study of interferon and sti571 (iris) trial. Haematologica, Jul 2009.
21. Shreya Kanodia, Eric Wieder, Sijie Lu, Moshe Talpaz, Gheath Alatrash, Karen Clise-Dwyer, and Jeffrey J Molldrem. Pr1-specific t cells are associated with un- maintained cytogenetic remission of chronic myelogenous leukemia after interferon withdrawal. PLoS One, 5(7):e11770, 2010.
22. Mhairi Copland, Ashley Hamilton, Lucy J Elrick, Janet W Baird, Elaine K Allan, Niove Jordanides, Martin Barow, Joanne C Mountford, and Tessa L Holyoake. Dasatinib (bms-354825) targets an earlier progenitor population than imatinib in primary cml but does not eliminate the quiescent fraction. Blood, 107(11):4532– 4539, Jun 2006.
23. Susan M Graham, Heather G J, Elaine Allan, Charlie Pearson, Michael J Alcorn, Linda Richmond, and Tessa L Holyoake. Primitive, quiescent, philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to sti571 in vitro. Blood, 99(1):319–325, Jan 2002.
24. Edurne San José-Eneriz, Xabier Agirre, Antonio Jiménez-Velasco, Lucia Cordeu, Vanesa Martín, Victor Arqueros, Leire Gárate, Vicente Fresquet, Francisco Cer- vantes, José A Martínez-Climent, Anabel Heiniger, Antonio Torres, Felipe Prósper, and Jose Roman-Gomez. Epigenetic down-regulation of bim expression is asso- ciated with reduced optimal responses to imatinib treatment in chronic myeloid leukaemia. Eur J Cancer, 45(10):1877–1889, Jul 2009.
25. Dianne S Schwarz, György Hutvágner, Tingting Du, Zuoshang Xu, Neil Aronin, and Phillip D Zamore. Asymmetry in the assembly of the rnai enzyme complex. Cell, 115(2):199–208, Oct 2003.
26. Ton van Agthoven, Jos Veldscholte, Marcel Smid, Thecla L A van Agthoven, Lilian Vreede, Marieke Broertjes, Ingrid de Vries, Danielle de Jong, Roya Sarwari, and Lambert C J Dorssers. Functional identification of genes causing estrogen independence of human breast cancer cells. Breast Cancer Res Treat, 114(1):23– 30, Mar 2009.
27. Stephen G O'Brien, François Guilhot, Richard A Larson, Insa Gathmann, Miche- le Baccarani, Francisco Cervantes, Jan J Cornelissen, Thomas Fischer, Andreas Hochhaus, Timothy Hughes, Klaus Lechner, Johan L Nielsen, Philippe Rousselot, Josy Reiffers, Giuseppe Saglio, John Shepherd, Bengt Simonsson, Alois Gratwohl, John M Goldman, Hagop Kantarjian, Kerry Taylor, Gregor Verhoef, Ann E Bolton, Renaud Capdeville, Brian J Druker, and I. R. I. S. Investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med, 348(11):994–1004, Mar 2003.
28. J. Hald, T. Galbo, C. Rescan, L. Radzikowski, A. E. Sprinkel, H. Heimberg, J. Ahnfelt-Rønne, J. Jensen, R. Scharfmann, G. Gradwohl, K. H. Kaestner, C. Sto- eckert, J. N. Jensen, and O. D. Madsen. Pancreatic islet and progenitor cell surface markers with cell sorting potential. Diabetologia, 55(1):154–165, Jan 2012.
29. Michele Baccarani, Giuseppe Saglio, John Goldman, Andreas Hochhaus, Bengt Simonsson, Frederick Appelbaum, Jane Apperley, Francisco Cervantes, Jorge Cor- tes, Michael Deininger, Alois Gratwohl, François Guilhot, Mary Horowitz, Timothy Hughes, Hagop Kantarjian, Richard Larson, Dietger Niederwieser, Richard Silver, Rudiger Hehlmann, and European LeukemiaNet. Evolving concepts in the mana- gement of chronic myeloid leukemia: recommendations from an expert panel on behalf of the european leukemianet. Blood, 108(6):1809–1820, Sep 2006.
30. A. Goga, J. McLaughlin, D. E. Afar, D. C. Saffran, and O. N. Witte. Alternative signals to ras for hematopoietic transformation by the bcr-abl oncogene. Cell, 82(6):981–988, Sep 1995.
31. D.A. Nowell, P. & Hungerford. A minute chromosome in human granulocytic leukemia. Science, 132:1497, 1960.
32. Eva Madi Riising and Kristian Helin. A new role for the polycomb group protein ezh1 in promoting transcription. Mol Cell, 45(2):145–146, Jan 2012.
33. J. J. Molldrem, P. P. Lee, C. Wang, R. E. Champlin, and M. M. Davis. A pr1- human leukocyte antigen-a2 tetramer can be used to isolate low-frequency cyto- toxic t lymphocytes from healthy donors that selectively lyse chronic myelogenous leukemia. Cancer Res, 59(11):2675–2681, Jun 1999.
34. Thijn R Brummelkamp, René Bernards, and Reuven Agami. A system for stable expression of short interfering rnas in mammalian cells. Science, 296(5567):550– 553, Apr 2002.
35. G. P. Amarante-Mendes, C. Naekyung Kim, L. Liu, Y. Huang, C. L. Perkins, D. R. Green, and K. Bhalla. Bcr-abl exerts its antiapoptotic effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrome c and activation of caspase-3. Blood, 91(5):1700–1705, Mar 1998.
36. A. M. Pendergast, L. A. Quilliam, L. D. Cripe, C. H. Bassing, Z. Dai, N. Li, A. Bat- zer, K. M. Rabun, C. J. Der, and J. Schlessinger. Bcr-abl-induced oncogenesis is mediated by direct interaction with the sh2 domain of the grb-2 adaptor protein. Cell, 75(1):175–185, Oct 1993.
37. D. D. De Carvalho, R. Binato, W. O. Pereira, J. M G Leroy, M. D. Colassanti, R. Proto-Siqueira, A. E B Bueno-Da-Silva, M. A. Zago, M. A. Zanichelli, E. Ab- delhay, F. A. Castro, J. F. Jacysyn, and G. P. Amarante-Mendes. Bcr-abl-mediated upregulation of prame is responsible for knocking down trail in cml patients. On- cogene, 30(2):223–233, Jan 2011.
38. D. Craigie. Case of disease of the spleen in which death took place from suppu- ration of the blood. Edinburgh Medical and Surgical Journal, 64:400–412, 1845.
39. Ellen Weisberg, Paul W Manley, Werner Breitenstein, Josef Br¸ggen, Sandra W Cowan-Jacob, Arghya Ray, Brian Huntly, Doriano Fabbro, Gabriele Fendrich, Eli- zabeth Hall-Meyers, Andrew L Kung, J¸rgen Mestan, George Q Daley, Linda Cal- lahan, Laurie Catley, Cara Cavazza, Mohammad Azam, Azam Mohammed, Donna Neuberg, Renee D Wright, D. Gary Gilliland, and James D Griffin. Characteriza- tion of amn107, a selective inhibitor of native and mutant bcr-abl. Cancer Cell, 7(2):129–141, Feb 2005.
40. Nobuhisa Ishikawa, Yataro Daigo, Atsushi Takano, Masaya Taniwaki, Tatsuya Ka- to, Sonosuke Tanaka, Wataru Yasui, Yukio Takeshima, Kouki Inai, Hitoshi Nishi- mura, Eiju Tsuchiya, Nobuoki Kohno, and Yusuke Nakamura. Characterization of sez6l2 cell-surface protein as a novel prognostic marker for lung cancer. Cancer Sci, 97(8):737–745, Aug 2006.
41. A. Burchert and A. Neubauer. [chronic myeloid leukemia. diagnostics, therapy and future strategy]. Internist (Berl), 52(3):283–93; quiz 294–5, Mar 2011.
42. M. E. Gorre, M. Mohammed, K. Ellwood, N. Hsu, R. Paquette, P. N. Rao, and C. L. Sawyers. Clinical resistance to sti-571 cancer therapy caused by bcr-abl gene mutation or amplification. Science, 293(5531):876–880, Aug 2001.
43. Louis J Lombardo, Francis Y Lee, Ping Chen, Derek Norris, Joel C Barrish, Ka- melia Behnia, Stephen Castaneda, Lyndon A M Cornelius, Jagabandhu Das, Ar- thur M Doweyko, Craig Fairchild, John T Hunt, Ivan Inigo, Kathy Johnston, Amrita Kamath, David Kan, Herbert Klei, Punit Marathe, Suhong Pang, Rus- sell Peterson, Sidney Pitt, Gary L Schieven, Robert J Schmidt, John Tokarski, Mei-Li Wen, John Wityak, and Robert M Borzilleri. Discovery of n-(2-chloro- 6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (bms-354825), a dual src/abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem, 47(27):6658–6661, Dec 2004.
44. F. Bonifazi, A. de Vivo, G. Rosti, F. Guilhot, J. Guilhot, E. Trabacchi, R. Hehl- mann, A. Hochhaus, P. C. Shepherd, J. L. Steegmann, H. C. Kluin-Nelemans, J. Thaler, B. Simonsson, A. Louwagie, J. Reiffers, F. X. Mahon, E. Montefusco, G. Alimena, J. Hasford, S. Richards, G. Saglio, N. Testoni, G. Martinelli, S. Tura, M. Baccarani, Europena Study Group on Interferon in Chronic Myeloid Leukemia, Italian Cooperative Study Group on CML, France Intergroup of CML, German CML Study Group, U. K. Medical Research Council Working Party on CML, Spa- nish CML Study Group, Australian CML Study Group, and Swedish CML Study Group. Chronic myeloid leukemia and interferon-alpha: a study of complete cyto- genetic responders. Blood, 98(10):3074–3081, Nov 2001.
45. J. J. Molldrem, P. P. Lee, C. Wang, K. Felio, H. M. Kantarjian, R. E. Champlin, and M. M. Davis. Evidence that specific t lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med, 6(9):1018–1023, Sep 2000.
46. Aimee L Jackson, Steven R Bartz, Janell Schelter, Sumire V Kobayashi, Julja Burchard, Mao Mao, Bin Li, Guy Cavet, and Peter S Linsley. Expression profiling reveals off-target gene regulation by rnai. Nat Biotechnol, 21(6):635–637, Jun 2003.
47. Angelique Schnerch, Jung Bok Lee, Monica Graham, Borhane Guezguez, and Mi- ckie Bhatia. Human embryonic stem cell-derived hematopoietic cells maintain core epigenetic machinery of the polycomb group/trithorax group complexes distinctly from functional adult hematopoietic stem cells. Stem Cells Dev, 22(1):73–89, Jan 2013.
48. Claude Preudhomme, Joëlle Guilhot, Franck Emmanuel Nicolini, Agnès Guerci- Bresler, Françoise Rigal-Huguet, Frederic Maloisel, Valérie Coiteux, Martine Gar- dembas, Christian Berthou, Anne Vekhoff, Delphine Rea, Eric Jourdan, Christian Allard, Alain Delmer, Philippe Rousselot, Laurence Legros, Marc Berger, Selim Corm, Gabriel Etienne, Catherine Roche-Lestienne, Virginie Eclache, François- Xavier Mahon, François Guilhot, S. P. I. R. I. T. Investigators, and France In- tergroupe des Leucémies Myéloïdes Chroniques (Fi-LMC). Imatinib plus pegin- terferon alfa-2a in chronic myeloid leukemia. N Engl J Med, 363(26):2511–2521, Dec 2010.
49. J. D. Rowley. Letter: A new consistent chromosomal abnormality in chronic mye- logenous leukaemia identified by quinacrine fluorescence and giemsa staining. Na- ture, 243(5405):290–293, Jun 1973.
50. M. Talpaz, K. B. McCredie, G. M. Mavligit, and J. U. Gutterman. Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia. Blood, 62(3):689–692, Sep 1983.
51. Ruibao Ren. Mechanisms of bcr-abl in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer, 5(3):172–183, Mar 2005.
52. Alfonso Quint·s-Cardama, Hagop M Kantarjian, and Jorge E Cortes. Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia. Can- cer Control, 16(2):122–131, Apr 2009.
53. Hagop Kantarjian, Francis Giles, Lydia Wunderle, Kapil Bhalla, Susan O'Brien, Barbara Wassmann, Chiaki Tanaka, Paul Manley, Patricia Rae, William Mietlow- ski, Kathy Bochinski, Andreas Hochhaus, James D Griffin, Dieter Hoelzer, Maher Albitar, Margaret Dugan, Jorge Cortes, Leila Alland, and Oliver G Ottmann. Ni- lotinib in imatinib-resistant cml and philadelphia chromosome-positive all. N Engl J Med, 354(24):2542–2551, Jun 2006.
54. W. C. Moloney. Radiogenic leukemia revisited. Blood, 70(4):905–908, Oct 1987.
55. R. Hehlmann, H. Heimpel, J. Hasford, H. J. Kolb, H. Pralle, D. K. Hossfeld, W. Queisser, H. Löffler, A. Hochhaus, and B. Heinze. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. the german cml study group. Blood, 84(12):4064–4077, Dec 1994.
56. Andreas Burchert, Martin C Müller, Philippe Kostrewa, Philipp Erben, Tilman Bostel, Simone Liebler, Rüdiger Hehlmann, Andreas Neubauer, and Andreas Hoch- haus. Sustained molecular response with interferon alfa maintenance after induc- tion therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia. J Clin Oncol, 28(8):1429–1435, Mar 2010.
57. Ton van Agthoven, Anieta M Sieuwerts, Marion E Meijer van Gelder, Maxime P Look, Marcel Smid, Jos Veldscholte, Stefan Sleijfer, John A Foekens, and Lambert C J Dorssers. Relevance of breast cancer antiestrogen resistance genes in human breast cancer progression and tamoxifen resistance. J Clin Oncol, 27(4):542–549, Feb 2009.
58. F. X. Mahon, M. W. Deininger, B. Schultheis, J. Chabrol, J. Reiffers, J. M. Gold- man, and J. V. Melo. Selection and characterization of bcr-abl positive cell lines with differential sensitivity to the tyrosine kinase inhibitor sti571: diverse mecha- nisms of resistance. Blood, 96(3):1070–1079, Aug 2000.
59. M. Nieborowska-Skorska, M. A. Wasik, A. Slupianek, P. Salomoni, T. Kitamura, B. Calabretta, and T. Skorski. Signal transducer and activator of transcription (stat)5 activation by bcr/abl is dependent on intact src homology (sh)3 and sh2 domains of bcr/abl and is required for leukemogenesis. J Exp Med, 189(8):1229– 1242, Apr 1999.
60. Daniel R Caffrey, Juan Zhao, Zhili Song, Michael E Schaffer, Steven A Haney, Romesh R Subramanian, Albert B Seymour, and Jason D Hughes. sirna off-target effects can be reduced at concentrations that match their individual potency. PLoS One, 6(7):e21503, 2011.
61. D. Cortez, G. Reuther, and A. M. Pendergast. The bcr-abl tyrosine kinase ac- tivates mitogenic signaling pathways and stimulates g1-to-s phase transition in hematopoietic cells. Oncogene, 15(19):2333–2342, Nov 1997.
62. Y. Ben-Neriah, G. Q. Daley, A. M. Mes-Masson, O. N. Witte, and D. Baltimore. The chronic myelogenous leukemia-specific p210 protein is the product of the bcr/abl hybrid gene. Science, 233(4760):212–214, Jul 1986.
63. Pablo Ramirez and John F DiPersio. Therapy options in imatinib failures. Onco- logist, 13(4):424–434, Apr 2008.
64. John S Tokarski, John A Newitt, Chieh Ying J Chang, Janet D Cheng, Michael Wittekind, Susan E Kiefer, Kevin Kish, Francis Y F Lee, Robert Borzillerri, Louis J Lombardo, Dianlin Xie, Yaqun Zhang, and Herbert E Klei. The structure of dasa- tinib (bms-354825) bound to activated abl kinase domain elucidates its inhibitory activity against imatinib-resistant abl mutants. Cancer Res, 66(11):5790–5797, Jun 2006.
65. F. Gizard, E. Teissier, I. Dufort, G. Luc, V. Luu-The, B. Staels, and D. W. Hum. The transcriptional regulating protein of 132 kda (trep-132) differentially influ- ences steroidogenic pathways in human adrenal nci-h295 cells. J Mol Endocrinol, 32(2):557–569, Apr 2004.
66. Florence Gizard, Romain Robillard, Olivier Barbier, Brigitte Quatannens, Anne Faucompré, Françoise Révillion, Jean-Philippe Peyrat, Bart Staels, and Dean W Hum. Trep-132 controls cell proliferation by regulating the expression of the cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1. Mol Cell Biol, 25(11):4335–4348, Jun 2005.
67. A. Hochhaus, S. G. O'Brien, F. Guilhot, B. J. Druker, S. Branford, L. Foroni, J. M. Goldman, M. C. Müller, J. P. Radich, M. Rudoltz, M. Mone, I. Gathmann, T. P. Hughes, R. A. Larson, and I. R. I. S. Investigators. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia, 23(6):1054–1061, Jun 2009.
68. Martin Sattler, M. Golam Mohi, Yuri B Pride, Laura R Quinnan, Nicole A Malouf, Klaus Podar, Franck Gesbert, Hiromi Iwasaki, Shaoguang Li, Richard A Van Etten, Haihua Gu, James D Griffin, and Benjamin G Neel. Critical role for gab2 in transformation by bcr/abl. Cancer Cell, 1(5):479–492, Jun 2002.
69. H. Konig, M. Holtz, H. Modi, P. Manley, T. L. Holyoake, S. J. Forman, and R. Bhatia. Enhanced bcr-abl kinase inhibition does not result in increased inhi- bition of downstream signaling pathways or increased growth suppression in cml progenitors. Leukemia, 22(4):748–755, Apr 2008.
70. Nikolas von Bubnoff, Simone Barwisch, Michael R Speicher, Christian Peschel, and Justus Duyster. A cell-based screening strategy that predicts mutations in oncogenic tyrosine kinases: implications for clinical resistance in targeted cancer treatment. Cell Cycle, 4(3):400–406, Mar 2005.
71. R. C. Lee, R. L. Feinbaum, and V. Ambros. The c. elegans heterochronic gene lin-4 encodes small rnas with antisense complementarity to lin-14. Cell, 75(5):843–854, Dec 1993.
72. J. H. Bennett. Case of hypertrophy of the spleen and liver in which death took place from suppuration of the blood. Edinburgh Medical and Surgical Journal, 64:413–423, 1845.
73. James W Vardiman, Nancy Lee Harris, and Richard D Brunning. The world health organization (who) classification of the myeloid neoplasms. Blood, 100(7):2292– 2302, Oct 2002.
74. Nikolas von Bubnoff, Darren R Veach, Heiko van der Kuip, Walter E Aulitzky, Jana Sänger, Petra Seipel, William G Bornmann, Christian Peschel, Bayard Clarkson, and Justus Duyster. A cell-based screen for resistance of bcr-abl-positive leukemia identifies the mutation pattern for pd166326, an alternative abl kinase inhibitor. Blood, 105(4):1652–1659, Feb 2005.
75. Ying Wang, Dali Cai, Cornelia Brendel, Christine Barett, Philipp Erben, Paul W Manley, Andreas Hochhaus, Andreas Neubauer, and Andreas Burchert. Adaptive secretion of granulocyte-macrophage colony-stimulating factor (gm-csf) mediates imatinib and nilotinib resistance in bcr/abl+ progenitors via jak-2/stat-5 pathway activation. Blood, 109(5):2147–2155, Mar 2007.
76. M. S. Holtz, S. J. Forman, and R. Bhatia. Nonproliferating cml cd34+ progeni- tors are resistant to apoptosis induced by a wide range of proapoptotic stimuli. Leukemia, 19(6):1034–1041, Jun 2005.
77. G. Laible, A. Wolf, R. Dorn, G. Reuter, C. Nislow, A. Lebersorger, D. Popkin, L. Pillus, and T. Jenuwein. Mammalian homologues of the polycomb-group gene enhancer of zeste mediate gene silencing in drosophila heterochromatin and at s. cerevisiae telomeres. EMBO J, 16(11):3219–3232, Jun 1997.
78. L. O'Connor, A. Strasser, L. A. O'Reilly, G. Hausmann, J. M. Adams, S. Cory, and D. C. Huang. Bim: a novel member of the bcl-2 family that promotes apoptosis. EMBO J, 17(2):384–395, Jan 1998.
79. Junya Kuroda, Hamsa Puthalakath, Mark S Cragg, Priscilla N Kelly, Philippe Bouillet, David C S Huang, Shinya Kimura, Oliver G Ottmann, Brian J Druker, Andreas Villunger, Andrew W Roberts, and Andreas Strasser. 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 U S A, 103(40):14907–14912, Oct 2006.
80. Natalia L Komarova and Dominik Wodarz. Effect of cellular quiescence on the success of targeted cml therapy. PLoS One, 2(10):e990, 2007.
81. C. L. Sawyers, J. McLaughlin, and O. N. Witte. Genetic requirement for ras in the transformation of fibroblasts and hematopoietic cells by the bcr-abl oncogene. J Exp Med, 181(1):307–313, Jan 1995.
82. E. Weisberg, P. Manley, J. Mestan, S. Cowan-Jacob, A. Ray, and J. D. Grif- fin. Amn107 (nilotinib): a novel and selective inhibitor of bcr-abl. Br J Cancer, 94(12):1765–1769, Jun 2006.
83. Xiaohua Shen, Yingchun Liu, Yu-Jung Hsu, Yuko Fujiwara, Jonghwan Kim, Xiao- hong Mao, Guo-Cheng Yuan, and Stuart H Orkin. Ezh1 mediates methylation on histone h3 lysine 27 and complements ezh2 in maintaining stem cell identity and executing pluripotency. Mol Cell, 32(4):491–502, Nov 2008.
84. Ravinesh A Kumar, Christian R Marshall, Judith A Badner, Timothy D Babatz, Zohar Mukamel, Kimberly A Aldinger, Jyotsna Sudi, Camille W Brune, Gerald Goh, Samer Karamohamed, James S Sutcliffe, Edwin H Cook, Daniel H Geschwind, William B Dobyns, Stephen W Scherer, and Susan L Christian. Association and mutation analyses of 16p11.2 autism candidate genes. PLoS One, 4(2):e4582, 2009.
85. Amie S Corbin, Anupriya Agarwal, Marc Loriaux, Jorge Cortes, Michael W Deinin- ger, and Brian J Druker. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of bcr-abl activity. J Clin Invest, 121(1):396–409, Jan 2011.
86. Rafael Bejar, Kristen Stevenson, Omar Abdel-Wahab, Naomi Galili, Björn Nilsson, Guillermo Garcia-Manero, Hagop Kantarjian, Azra Raza, Ross L Levine, Donna Neuberg, and Benjamin L Ebert. Clinical effect of point mutations in myelodys- plastic syndromes. N Engl J Med, 364(26):2496–2506, Jun 2011.
87. Jirair K Bedoyan, Ravinesh A Kumar, Jyotsna Sudi, Faye Silverstein, Todd Ackley, Ramaswamy K Iyer, Susan L Christian, and Donna M Martin. Duplication 16p11.2 in a child with infantile seizure disorder. Am J Med Genet A, 152A(6):1567–1574, Jun 2010.
88. Raphael Margueron, Guohong Li, Kavitha Sarma, Alexandre Blais, Jiri Zavadil, Christopher L Woodcock, Brian D Dynlacht, and Danny Reinberg. Ezh1 and ezh2 maintain repressive chromatin through different mechanisms. Mol Cell, 32(4):503– 518, Nov 2008.
89. L. Puil, J. Liu, G. Gish, G. Mbamalu, D. Bowtell, P. G. Pelicci, R. Arlinghaus, and T. Pawson. Bcr-abl oncoproteins bind directly to activators of the ras signalling pathway. EMBO J, 13(4):764–773, Feb 1994.
90. Andrew I Su, Tim Wiltshire, Serge Batalov, Hilmar Lapp, Keith A Ching, David Block, Jie Zhang, Richard Soden, Mimi Hayakawa, Gabriel Kreiman, Michael P Cooke, John R Walker, and John B Hogenesch. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A, 101(16):6062– 6067, Apr 2004.
91. Moshe Talpaz, Neil P Shah, Hagop Kantarjian, Nicholas Donato, John Nicoll, Ron Paquette, Jorge Cortes, Susan O'Brien, Claude Nicaise, Eric Bleickardt, M. Anne Blackwood-Chirchir, Vishwanath Iyer, Tai-Tsang Chen, Fei Huang, Ar- thur P Decillis, and Charles L Sawyers. Dasatinib in imatinib-resistant philadelphia chromosome-positive leukemias. N Engl J Med, 354(24):2531–2541, Jun 2006.
92. Kambiz Mousavi, Hossein Zare, A. Hongjun Wang, and Vittorio Sartorelli. Poly- comb protein ezh1 promotes rna polymerase ii elongation. Mol Cell, 45(2):255– 262, Jan 2012.
93. Katrien Berns, Hugo M Horlings, Bryan T Hennessy, Mandy Madiredjo, E. Marielle Hijmans, Karin Beelen, Sabine C Linn, Ana Maria Gonzalez-Angulo, Katherine Stemke-Hale, Michael Hauptmann, Roderick L Beijersbergen, Gordon B Mills, Marc J van de Vijver, and René Bernards. A functional genetic approach identifies the pi3k pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell, 12(4):395–402, Oct 2007.
94. Neil P Shah, Chris Tran, Francis Y Lee, Ping Chen, Derek Norris, and Charles L Sawyers. Overriding imatinib resistance with a novel abl kinase inhibitor. Science, 305(5682):399–401, Jul 2004.
95. Diego Pasini, Adrian P Bracken, and Kristian Helin. Polycomb group proteins in cell cycle progression and cancer. Cell Cycle, 3(4):396–400, Apr 2004.

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