Oncogenic RAS enables DNA damage- and p53-dependent differentiation of acute myeloid leukemia cells in response to chemotherapy

PLoS ONE

Volumn 4, Issue 11, 2009, Pages

  Meyer, Mona ^a   Rübsamen, Daniela ^a   Slany, Robert ^b   Illmer, Thomas ^c   Stabla, Kathleen ^a   Roth, Petra ^a   Stiewe, Thorsten ^a   Eilers, Martin ^d   Neubauer, Andreas ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^c DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^d UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

4 HYDROXYTAMOXIFEN; ANTINEOPLASTIC AGENT; CYTARABINE; CYTOTOXIC AGENT; DAUNORUBICIN; DNA; ETOPOSIDE; NUTLIN 3; PROTEIN MDM2; PROTEIN P53; RAS PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BONE MARROW CELL; CANCER INHIBITION; CELL DIFFERENTIATION; CELL ONCOGENE; CLONOGENESIS; CONTROLLED STUDY; DNA DAMAGE; DRUG PROTEIN BINDING; ENZYME ACTIVATION; GENE EXPRESSION; LEUKEMIA CELL; LEUKEMOGENESIS; MOUSE; NONHUMAN; PROTEIN DEGRADATION; PROTEIN INDUCTION; APOPTOSIS; CELL AGING; CELL PROLIFERATION; CYTOLOGY; GENETICS; HUMAN; METABOLISM; MUTATION; ONCOGENE RAS;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BONE MARROW CELLS; CELL AGING; CELL DIFFERENTIATION; CELL PROLIFERATION; CYTARABINE; DAUNORUBICIN; ETOPOSIDE; GENES, RAS; HUMANS; LEUKEMIA, MYELOID, ACUTE; MUTATION; RAS PROTEINS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 70450164376     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0007768     Document Type: Article

References (59)

1. Schlenk RF, Dohner K, Krauter J, Frohling S, Corbacioglu A, et al. (2008) Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 358: 1909-1918.
2. Tallman MS, Gilliland DG, Rowe JM (2005) Drug therapy for acute myeloid leukemia. Blood 106: 1154-1163.
3. Frohling S, Scholl C, Gilliland DG, Levine RL (2005) Genetics of myeloid malignancies: pathogenetic and clinical implications. J Clin Oncol 23: 6285-6295.
4. Mayer R, Davis R, Schiffer C, Berg D, Powell B, et al. (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia: Cancer and Leukemia Group B. New England Journal of Medicine 331: 896-903.
5. Estey E, Dohner H (2006) Acute myeloid leukaemia. Lancet 368: 1894-1907.
6. Bos JL (1989) ras oncogenes in human cancer: A review. Cancer Research 49: 4682-4689.
7. Larsen J, Beug H, Hayman MJ (1992) The v-ski oncogene cooperates with the v-sea oncogene in erythroid transformation by blocking erythroid differentiation. Oncogene 7: 1903-1911.
8. MacKenzie KL, Dolnikov A, Millington M, Shounan Y, Symonds G (1999) Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow repopulated mice. Blood 93: 2043-2056.
9. Braun BS, Tuveson DA, Kong N, Le DT, Kogan SC, et al. (2004) Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci U S A 101: 597-602.
10. Chan IT, Kutok JL, Williams IR, Cohen S, Kelly L, et al. (2004) Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. J Clin Invest 113: 528-538.
11. Parikh C, Subrahmanyam R, Ren R (2006) Oncogenic NRAS rapidly and efficiently induces CMML- and AML-like diseases in mice. Blood 108: 2349-2357.
12. Braun BS, Archard JA, Van Ziffle JA, Tuveson DA, Jacks TE, et al. (2006) Somatic activation of a conditional KrasG12D allele causes ineffective erythropoiesis in vivo. Blood 108: 2041-2044.
13. Chan IT, Kutok JL, Williams IR, Cohen S, Moore S, et al. (2006) Oncogenic K-ras cooperates with PML-RAR alpha to induce an acute promyelocytic leukemia-like disease. Blood 108: 1708-1715.
14. Hibi S, Loehler J, Friel J, Stocking C, Ostertag W (1993) Induction of monocytic differentiation and tumorigenicity by v-Ha-ras in differentiation-arrested hematopoietic cells. Blood 81: 1841-1848.
15. Hawley RG, Fong AZ, Ngan BY, Hawley TS (1995) Hematopoietic transforming potential of activated ras in chimeric mice. Oncogene 11: 1113-1123.
16. Darley RL, Burnett AK (1999) Mutant RAS inhibits neutrophil but not macrophage differentiation and allows continued growth of neutrophil precursors. Exp Hematol 27: 1599-1608.
17. Shen SW, Dolnikov A, Passioura T, Millington M, Wotherspoon S, et al. (2004) Mutant N-ras preferentially drives human CD34+ hematopoietic progenitor cells into myeloid differentiation and proliferation both in vitro and in the NOD/SCID mouse. Exp Hematol 32: 852-860.
18. Shen S, Passioura T, Symonds G, Dolnikov A (2007) N-ras oncogene-induced gene expression in human hematopoietic progenitor cells: upregulation of p16INK4a and p21CIP1/WAF1 correlates with myeloid differentiation. Exp Hematol 35: 908-919.
19. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88: 593-602.
20. Groth A, Weber JD, Willumsen BM, Sherr CJ, Roussel MF (2000) Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. J Biol Chem 275: 27473-27480.
21. Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, et al. (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436: 720-724.
22. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, et al. (2005) Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436: 660-665.
23. Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, et al. (2005) Tumour biology: senescence in premalignant tumours. Nature 436: 642.
24. Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, et al. (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444: 638-642.
25. Fikaris AJ, Lewis AE, Abulaiti A, Tsygankova OM, Meinkoth JL (2006) Ras triggers ataxia-telangiectasia-mutated and Rad-3-related activation and apoptosis through sustained mitogenic signaling. J Biol Chem 281: 34759-34767.
26. Neubauer A, Maharry K, Mrozek K, Thiede C, Marcucci G, et al. (2008) Patients with acute myeloid leukemia and RAS mutations benefit most from postremission high-dose cytarabine: A Cancer and Leukemia Group B study. J Clin Oncol 26: 4603-4609.
27. Zeisig BB, Garcia-Cuellar MP, Winkler TH, Slany RK (2003) The oncoprotein MLL-ENL disturbs hematopoietic lineage determination and transforms a biphenotypic lymphoid/myeloid cell. Oncogene 22: 1629-1637.
28. Zeisig BB, Milne T, Garcia-Cuellar MP, Schreiner S, Martin ME, et al. (2004) Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol 24: 617-628.
29. Collado M, Serrano M (2006) The power and the promise of oncogene-induced senescence markers. Nat Rev Cancer 6: 472-476.
30. Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, et al. (1997) Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell 91: 649-659.
31. Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, et al. (2005) DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434: 864-870.
32. Shen WPV, Alfrich TH, Venta-Perez G, Franza BR, Furth ME (1987) Expression of normal and mutant ras proteins in human acute leukemia. Oncogene 1: 157-165.
33. Nagler A, Kletter Y, Ricklis I, Gazit E, Tatarsky I, et al. (1986) Effect of cytosine arabinoside on differentiation of normal human bone marrow cells. Exp Hematol 14: 241-245.
34. Sarkaria JN, Busby EC, Tibbetts RS, Roos P, Taya Y, et al. (1999) Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res 59: 4375-4382.
35. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, et al. (2002) A stem cell molecular signature. Science 298: 601-604.
36. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102: 15545-15550.
37. Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, et al. (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269: 1281-1284.
38. Gottlieb E, Haffner R, von Ruden T, Wagner EF, Oren M (1994) Down-regulation of wild-type p53 activity interferes with apoptosis of IL-3-dependent hematopoietic cells following IL-3 withdrawal. Embo J 13: 1368-1374.
39. Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, et al. (1999) A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285: 1733-1737.
40. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, et al. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303: 844-848.
41. Kojima K, Konopleva M, Samudio IJ, Shikami M, Cabreira-Hansen M, et al. (2005) MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy. Blood 106: 3150-3159.
42. Kojima K, Konopleva M, McQueen T, O'Brien S, Plunkett W, et al. (2006) Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia. Blood 108: 993-1000.
43. Gu L, Zhu N, Findley HW, Zhou M (2008) MDM2 antagonist nutlin-3 is a potent inducer of apoptosis in pediatric acute lymphoblastic leukemia cells with wild-type p53 and overexpression of MDM2. Leukemia 22: 730-739.
44. Secchiero P, Zerbinati C, Melloni E, Milani D, Campioni D, et al. (2007) The MDM-2 antagonist nutlin-3 promotes the maturation of acute myeloid leukemic blasts. Neoplasia 9: 853-861.
45. Radich JP, Kopecky KJ, Appelbaum F, Willman CL, Collins SJ (1992) N-ras mutations in acute myelogeneous leukemia: A review of the current literature and an update ot the Southwest Oncology Group experience. Leukemia and Lymphoma 6: 325-334.
46. Paquette RL, Landaw EM, Pierre RV, Kahan J, Luebbert M, et al. (1993) N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndromes. Blood 82: 590-599.
47. Coghlan D, Morley AA, Matthews JP, Bishop JF (1994) The incidence and prognostic significance of mutations in codon 13 of the N-ras gene in acute myeloid leukemia. Leukemia 8: 1682-1687.
48. Neubauer A, Dodge R, George SL, Davey FR, Silver RT, et al. (1994) Prognostic importance of mutations in the ras protooncogenes in de novo acute myeloid leukemia. Blood 83: 1603-1611.
49. Illmer T, Thiede C, Fredersdorf A, Stadler S, Neubauer A, et al. (2005) Activation of the RAS pathway is predictive for a chemosensitive phenotype of acute myelogenous leukemia blasts. Clin Cancer Res 11: 3217-3224.
50. Bacher U, Haferlach T, Schoch C, Kern W, Schnittger S (2006) Implications of NRAS mutations in AML: a study of 2502 patients. Blood 107: 3847-3853.
51. Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, et al. (2003) Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 17: 3029-3035.
52. Barabe F, Kennedy JA, Hope KJ, Dick JE (2007) Modeling the initiation and progression of human acute leukemia in mice. Science 316: 600-604.
53. Capizzi RL (1996) Curative chemotherapy for acute myeloid leukemia: the development of high-dose ara-C from the laboratory to bedside. Invest New Drugs 14: 249-256.
54. Abulaiti A, Fikaris AJ, Tsygankova OM, Meinkoth JL (2006) Ras induces chromosome instability and abrogation of the DNA damage response. Cancer Res 66: 10505-10512.
55. Huang CL, Deng ML, Guo RJ, Wu MT, Liu FZ, et al. (1988) A study on the induction of differentiation of human leukemic cells by harringtonine combined with cytarabine. Leukemia 2: 518-522.
56. Wiederschain D, Kawai H, Shilatifard A, Yuan ZM (2005) Multiple mixed lineage leukemia (MLL) fusion proteins suppress p53-mediated response to DNA damage. J Biol Chem 280: 24315-24321.
57. Potenza N, Vecchione C, Notte A, De Rienzo A, Rosica A, et al. (2005) Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice. EMBO Rep 6: 432-437.
58. Schreiner S, Birke M, Garcia-Cuellar MP, Zilles O, Greil J, et al. (2001) MLL-ENL causes a reversible and myc-dependent block of myelomonocytic cell differentiation. Cancer Res 61: 6480-6486.
59. Dimri GP, Lee X, Basile G, Acosta M, Scott G, et al. (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92: 9363-9367.