Blocking ETV6/RUNX1-induced MDM2 overexpression by Nutlin-3 reactivates p53 signaling in childhood leukemia

Leukemia

Volumn 28, Issue 3, 2014, Pages 600-608

  Kaindl, U ^a   Morak, M ^a   Portsmouth, C ^a   Mecklenbrauker A ^a   Kauer, M ^a   Zeginigg, M ^a   Attarbaschi, A ^b   Haas, O A ^a,b   Panzer Grumayer R ^a  

^a CHILDREN'S CANCER RESEARCH INSTITUTE   (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

ETV6 RUNX1 targets; ETV6 RUNX1 positive leukemia; MDM2; Nutlin 3; p53 pathway

Indexed keywords

CASPASE 3; NUTLIN 3; POLY(ADENOSINE DIPHOSPHATE RIBOSE); PROTEIN BAX; PROTEIN MDM2; PROTEIN P53; PUMA PROTEIN; TRANSCRIPTION FACTOR ETV6; TRANSCRIPTION FACTOR RUNX1;

APOPTOSIS; ARTICLE; CANCER CELL; CELL CYCLE; CHILD; CHILDHOOD LEUKEMIA; DNA DAMAGE; ENZYME ACTIVATION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; UPREGULATION;

APOPTOSIS; CHILD; CHROMATIN IMMUNOPRECIPITATION; CORE BINDING FACTOR ALPHA 2 SUBUNIT; HUMANS; IMIDAZOLES; PIPERAZINES; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROTO-ONCOGENE PROTEINS C-ETS; PROTO-ONCOGENE PROTEINS C-MDM2; REAL-TIME POLYMERASE CHAIN REACTION; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; TRANSCRIPTION, GENETIC; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84895828903     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2013.345     Document Type: Article

References (46)

1. Pui CH, Carroll WL, Meshinchi S, Arceci RJ. Biology, risk stratification, and therapy of pediatric acute leukemias: An update. J Clin Oncol 2011; 29: 551-565.
2. Zelent A, Greaves M, Enver T. Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia. Oncogene 2004; 23: 4275-4283.
3. Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, Moricke A et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: Results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 2010; 115: 3206-3214.
4. Kuster L, Grausenburger R, Fuka G, Kaindl U, Krapf G, Inthal A et al. ETV6/RUNX1-positive relapses evolve from an ancestral clone and frequently acquire deletions of genes implicated in glucocorticoid signaling. Blood 2011; 117: 2658-2667.
5. Malempati S, Gaynon PS, Sather H, La MK, Stork LC. Outcome after relapse among children with standard-risk acute lymphoblastic leukemia: Children's Oncology Group study CCG-1952. J Clin Oncol 2007; 25: 5800-5807.
6. Diakos C, Krapf G, Gerner C, Inthal A, Lemberger C, Ban J et al. RNAi-mediated silencing of TEL/AML1 reveals a heat-shock protein- and survivin-dependent mechanism for survival. Blood 2007; 109: 2607-2610.
7. Diakos C, Zhong S, Xiao Y, Zhou M, Vasconcelos GM, Krapf G et al. TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a. Blood 2010; 116: 4885-4893.
8. Schindler JW, Van Buren D, Foudi A, Krejci O, Qin J, Orkin SH et al. TEL-AML1 corrupts hematopoietic stem cells to persist in the bone marrow and initiate leukemia. Cell Stem Cell 2009; 5: 43-53.
9. Hong D, Gupta R, Ancliff P, Atzberger A, Brown J, Soneji S et al. Initiating and cancer-propagating cells in TEL-AML1-Associated childhood leukemia. Science 2008; 319: 336-339.
10. Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007; 446: 758-764.
11. Fuka G, Kantner HP, Grausenburger R, Inthal A, Bauer E, Krapf G et al. Silencing of ETV6/RUNX1 abrogates PI3K/AKT/mTOR signaling and impairs reconstitution of leukemia in xenografts. Leukemia 2012; 26: 927-933.
12. Fuka G, Kauer M, Kofler R, Haas OA, Panzer-Grumayer R. The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression. PLoS One 2011; 6: E26348.
13. Wade M, Li YC, Wahl GM. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 2013; 13: 83-96.
14. Brown CJ, Lain S, Verma CS, Fersht AR, Lane DP. Awakening guardian angels: Drugging the p53 pathway. Nat Rev Cancer 2009; 9: 862-873.
15. Cheok CF, Verma CS, Baselga J, Lane DP. Translating p53 into the clinic. Nat Rev Clin Oncol 2011; 8: 25-37.
16. Hof J, Krentz S, van Schewick C, Korner G, Shalapour S, Rhein P et al. Mutations and deletions of the TP53 gene predict nonresponse to treatment and poor outcome in first relapse of childhood acute lymphoblastic leukemia. J Clin Oncol 2011; 29: 3185-3193.
17. Zhang J, Mullighan CG, Harvey RC, Wu G, Chen X, Edmonson M et al. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: A report from the Children's Oncology Group. Blood 2011; 118: 3080-3087.
18. Fears S, Vignon C, Bohlander SK, Smith S, Rowley JD, Nucifora G. Correlation between the ETV6/CBFA2 (TEL/AML1) fusion gene and karyotypic abnormalities in children with B-cell precursor acute lymphoblastic leukemia. Genes Chromosomes Cancer 1996; 17: 127-135.
19. Kim DH, Moldwin RL, Vignon C, Bohlander SK, Suto Y, Giordano L et al. TEL-AML1 translocations with TEL and CDKN2 inactivation in acute lymphoblastic leukemia cell lines. Blood 1996; 88: 785-794.
20. Krapf G, Kaindl U, Kilbey A, Fuka G, Inthal A, Joas R et al. ETV6/RUNX1 abrogates mitotic checkpoint function and targets its key player MAD2L1. Oncogene 2010; 29: 3307-3312.
21. Phelps M, Darley M, Primrose JN, Blaydes JP. p53-independent activation of the hdm2-P2 promoter through multiple transcription factor response elements results in elevated hdm2 expression in estrogen receptor alpha-positive breast cancer cells. Cancer Res 2003; 63: 2616-2623.
22. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S et al. Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol 2004; 5: R80.
23. Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: A genome-wide classification study. Lancet Oncol 2009; 10: 125-134.
24. Wu Z, Irizarry RA, Gentleman R, Martinez-Murillo F, Spencer F. A model-based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc 2004; 99: 909-917.
25. Wettenhall JM, Smyth GK. LimmaGUI: A graphical user interface for linear modeling of microarray data. Bioinformatics 2004; 20: 3705-3706.
26. Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 2008; 9: 402-412.
27. Bartel F, Taubert H, Harris LC. Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell 2002; 2: 9-15.
28. Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP et al. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998; 282: 1497-1501.
29. Hiebert SW, Sun W, Davis JN, Golub T, Shurtleff S, Buijs A et al. The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription. Mol Cell Biol 1996; 16: 1349-1355.
30. Morrow M, Samanta A, Kioussis D, Brady HJ, Williams O. TEL-AML1 preleukemic activity requires the DNA binding domain of AML1 and the dimerization and corepressor binding domains of TEL. Oncogene 2007; 26: 4404-4414.
31. Wotton S, Terry A, Kilbey A, Jenkins A, Herzyk P, Cameron E et al. Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival. Oncogene 2008; 27: 5856-5866.
32. Inthal A, Krapf G, Beck D, Joas R, Kauer MO, Orel L et al. Role of the erythropoietin receptor in ETV6/RUNX1-positive acute lymphoblastic leukemia. Clin Cancer Res 2008; 14: 7196-7204.
33. Torrano V, Procter J, Cardus P, Greaves M, Ford A. ETV6-RUNX1 promotes survival of early B lineage progenitor cells via a dysregulated erythropoietin receptor. Blood 2011; 118: 4910-4918.
34. Xu-Monette ZY, Medeiros LJ, Li Y, Orlowski RZ, Andreeff M, Bueso-Ramos CE et al. Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood 2012; 119: 3668-3683.
35. Pant V, Quintas-Cardama A, Lozano G. The p53 pathway in hematopoiesis: Lessons from mouse models, implications for humans. Blood 2012; 120: 5118-5127.
36. Ramakers-van Woerden NL, Pieters R, Loonen AH, Hubeek I, van Drunen E, Beverloo HB et al. TEL/AML1 gene fusion is related to in vitro drug sensitivity for L- asparaginase in childhood acute lymphoblastic leukemia. Blood 2000; 96: 1094-1099.
37. Naderi EH, Findley HW, Ruud E, Blomhoff HK, Naderi S. Activation of cAMP signaling inhibits DNA damage-induced apoptosis in BCP-ALL cells through abrogation of p53 accumulation. Blood 2009; 114: 608-618.
38. Frost BM, Forestier E, Gustafsson G, Nygren P, Hellebostad M, Jonsson OG et al. Translocation t(12;21) is related to in vitro cellular drug sensitivity to doxorubicin and etoposide in childhood acute lymphoblastic leukemia. Blood 2004; 104: 2452-2457.
39. Pui CH, Relling MV, Downing Jr. Acute lymphoblastic leukemia. N Engl J Med 2004; 350: 1535-1548.
40. van Delft FW, Horsley S, Colman S, Anderson K, Bateman C, Kempski H et al. Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia. Blood 2011; 117: 6247-6254.
41. Lilljebjorn H, Soneson C, Andersson A, Heldrup J, Behrendtz M, Kawamata N et al. The correlation pattern of acquired copy number changes in 164 ETV6/RUNX1-positive childhood acute lymphoblastic leukemias. Hum Mol Genet 2010; 19: 3150-3158.
42. Wilson NK, Foster SD, Wang X, Knezevic K, Schutte J, Kaimakis P et al. Combinatorial transcriptional control in blood stem/progenitor cells: Genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell 2010; 7: 532-544.
43. Tijssen MR, Cvejic A, Joshi A, Hannah RL, Ferreira R, Forrai A et al. Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators. Dev Cell 2011; 20: 597-609.
44. Gu L, Zhu N, Findley HW, Zhou M. MDM2 antagonist nutlin-3 is a potent inducer of apoptosis in pediatric acute lymphoblastic leukemia cells with wild-Type p53and overexpression of MDM2. Leukemia 2008; 22: 730-739.
45. Abdul-Nabi AM, Yassin ER, Varghese N, Deshmukh H, Yaseen NR. In vitro transformation of primary human CD34þ cells by AML fusion oncogenes: Early gene expression profiling reveals possible drug target in AML. PLoS One 2010; 5: E12464.
46. Kojima K, Shimanuki M, Shikami M, Samudio IJ, Ruvolo V, Corn P et al. The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-Type AML. Leukemia 2008; 22: 1728-1736..