Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia

Blood

Volumn 111, Issue 3, 2008, Pages 1584-1593

  Saddler, Chris ^a   Ouillette, Peter ^a   Kujawski, Lisa ^a   Shangary, Sanjeev ^a   Talpaz, Moshe ^a   Kaminski, Mark ^a   Erba, Harry ^a   Shedden, Kerby ^b   Wang, Shaomeng ^a   Malek, Sami N ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; MI 63; NUTLIN 3; PROTEIN INHIBITOR; PROTEIN KINASE ZAP 70; PROTEIN MDM2; PROTEIN P53; PURINE DERIVATIVE; UNCLASSIFIED DRUG;

ADULT; AGED; ALLELE; ARTICLE; CHROMOSOME ABERRATION; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; FEMALE; GENE DELETION; GENE MUTATION; GENETIC ANALYSIS; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT RESPONSE;

EID: 38949135181     PISSN: 00064971     EISSN: 00064971     Source Type: Journal    
DOI: 10.1182/blood-2007-09-112698     Document Type: Article

References (61)

1. Chiorazzi N, Allen SL, Ferrarini M. Clinical and laboratory parameters that define clinically relevant B-CLL subgroups. Curr Top Microbiol Immunol. 2005;294:109-133.
2. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005;352:804-815.
3. Wierda W, O'Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005;23:4070-4078.
4. Keating MJ, O'Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005;23:4079-4088.
5. Byrd JC, Rai K, Peterson BL, et al. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005;105:49-53.
6. Vassilev LT. MDM2 inhibitors for cancer therapy. Trends Mol Med. 2007;13:23-31.
7. Toledo F, Wahl GM. MDM2 and MDM4: p53 regulators as targets in anticancer therapy. Int J Biochem Cell Biol. 2007;39:1476-1482.
8. Yang Y, Ludwig RL, Jensen JP, et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell. 2005;7:547-559.
9. Fotouhi N, Graves B. Small molecule inhibitors of p53/MDM2 interaction. Curr Top Med Chem. 2005;5:159-165.
10. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10:789-799.
11. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004;303:844-848.
12. Vassilev LT. Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics. Cell Cycle. 2004;3:419-421.
13. Wasylyk C, Salvi R, Argentini M, et al. p53 mediated death of cells overexpressing MDM2 by an inhibitor of MDM2 interaction with p53. Oncogene. 1999;18:1921-1934.
14. Lane DP, Fischer PM. Turning the key on p53. Nature. 2004;427:789-790.
15. Ding K, Lu Y, Nikolovska-Coleska Z, et al. Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. J Med Chem. 2006;49:3432-3435.
16. Ding K, Lu Y, Nikolovska-Coleska Z, et al. Structure-based design of potent non-peptide MDM2 inhibitors. J Am Chem Soc. 2005;127:10130-10131.
17. Lu Y, Nikolovska-Coleska Z, Fang X, et al. Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53 interaction through an integrated, virtual database screening strategy. J Med Chem. 2006;49:3759-3762.
18. Koblish HK, Zhao S, Franks CF, et al. Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo. Mol Cancer Ther. 2006;5:160-169.
19. Chen L, Yin H, Farooqi B, Sebti S, Hamilton AD, Chen J. p53 alpha-Helix mimetics antagonize p53/MDM2 interaction and activate p53. Mol Cancer Ther. 2005;4:1019-1025.
20. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature. 1997;387:296-299.
21. Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1997;420:25-27.
22. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature. 1997;387:299-303.
23. Secchiero P, Corallini F, Gonelli A, et al. Antiangiogenic activity of the MDM2 antagonist nutlin-3. Circ Res. 2007;100:61-69.
24. Efeyan A, Ortega-Molina A, Velasco-Miguel S, Herranz D, Vassilev LT, Serrano M. Induction of p53-dependent senescence by the MDM2 antagonist nutlin-3a in mouse cells of fibroblast origin. Cancer Res. 2007;67:7350-7357.
25. Gaidano G, Ballerini P, Gong JZ, et al. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 1991;88:5413-5417.
26. Wattel E, Preudhomme C, Hecquet B, et al. p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood. 1994;84:3148-3157.
27. Dohner H, Fischer K, Bentz M, et al. p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood. 1995;85:1580-1589.
28. Cordone I, Masi S, Mauro FR, et al. p53 expression in B-cell chronic lymphocytic leukemia: a marker of disease progression and poor prognosis. Blood. 1998;91:4342-4349.
29. Grever MR, Lucas DM, Dewald GW, et al. Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. J Clin Oncol. 2007;25:799-804.
30. Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100:4325-4336.
31. Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94:1840-1847.
32. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94:1848-1854.
33. Crespo M, Bosch F, Villamor N, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med. 2003;348:1764-1775.
34. Austen B, Powell JE, Alvi A, et al. Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood. 2005;106:3175-3182.
35. Wiestner A, Rosenwald A, Barry TS, et al. ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood. 2003;101:4944-4951.
36. Rassenti LZ, Huynh L, Toy TL, et al. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med. 2004;351:893-901.
37. Oscier DG, Gardiner AC, Mould SJ, et al. Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood. 2002;100:1177-1184.
38. Del Principe MI, Del Poeta G, Buccisano F, et al. Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood. 2006;108:853-861.
39. Orchard JA, Ibbotson RE, Davis Z, et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet. 2004;363:105-111.
40. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343:1910-1916.
41. Shanafelt TD, Witzig TE, Fink SR, et al. Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia. J Clin Oncol. 2006;24:4634-4641.
42. Zhao X, Li C, Paez JG, et al. An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res. 2004;64:3060-3071.
43. Nannya Y, Sanada M, Nakazaki K, et al. A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays. Cancer Res. 2005;65:6071-6079.
44. Di X, Matsuzaki H, Webster TA, et al. Dynamic model based algorithms for screening and genotyping over 100 K SNPs on oligonucleotide microarrays. Bioinformatics. 2005;21:1958-1963.
45. Pfeifer D, Pantic M, Skatulla I, et al. Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays. Blood. 2007;109:1202-1210.
46. Matsuzaki H, Dong S, Loi H, et al. Genotyping over 100,000 SNPs on a pair of oligonucleotide arrays. Nat Methods. 2004;1:109-111.
47. Ross CW, Ouillette PD, Saddler CM, Shedden KA, Malek SN. Comprehensive analysis of copy number and allele status identifies multiple chromosome defects underlying follicular lymphoma pathogenesis. Clin Cancer Res. 2007;13:4777-4785.
48. Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990-4997.
49. Ouillette P, Erba H, Kujawski L, Kaminski M, Shedden K, Malek S. Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Research. 2008;68(4).
50. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46:219-234.
51. Lin M, Wei LJ, Sellers WR, Lieberfarb M, Wong WH, Li C. dChipSNP: significance curve and clustering of SNP-array-based loss-of-heterozygosity data. Bioinformatics. 2004;20:1233-1240.
52. Matthews C, Catherwood M, Morris TC, Alexander HD. Routine analysis of IgVH mutational status in CLL patients using BIOMED-2 standardized primers and protocols. Leuk Lymphoma. 2004;45:1899-1904.
53. Tovar C, Rosinski J, Filipovic Z, et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006;103:1888-1893.
54. Hu B, Gilkes DM, Farooqi B, Sebti SM, Chen J. MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem. 2006;281:33030-33035.
55. Coll-Mulet L, Iglesias-Serret D, Santidrian AF, et al. MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood. 2006;107:4109-4114.
56. Watanabe T, Ichikawa A, Saito H, Hotta T. Over-expression of the MDM2 oncogene in leukemia and lymphoma. Leuk Lymphoma. 1996;21:391-397, color plates XVI following 395.
57. Pomerantz J, Schreiber-Agus N, Liegeois NJ, et al. The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell. 1998;92:713-723.
58. Pettitt AR, Sherrington PD, Stewart G, Cawley JC, Taylor AM, Stankovic T. p53 dysfunction in B-cell chronic lymphocytic leukemia: inactivation of ATM as an alternative to TP53 mutation. Blood. 2001;98:814-822.
59. Secchiero P, Barbarotto E, Tiribelli M, et al. Functional integrity of the p53-mediated apoptotic pathway induced by the non-genotoxic agent nutlin-3a in B-cell chronic lymphocytic leukemia (BCLL). Blood. 2006;107:4122-4129.
60. Kojima K, Konopleva M, McQueen T, O'Brien S, Plunkett W, Andreeff M. 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. 2006;108:993-1000.
61. Thornton PD, Gruszka-Westwood AM, Hamoudi RA, et al. Characterisation of TP53 abnormalities in chronic lymphocytic leukaemia. Hematol J. 2004;5:47-54.