TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 40, 2013, Pages 16127-16132

  Caceres, Gisela ^a   McGraw, Kathy ^a,b   Yip, Bon Ham ^c   Pellagatti, Andrea ^c   Johnson, Joseph ^a   Zhang, Ling ^a   Liu, Kenian ^a   Zhang, Lan Min ^a   Fulp, William J ^a   Lee, Ji Hyun ^a   Al Ali, Najla H ^a   Basiorka, Ashley ^a   Smith, Larry J ^d   Daugherty, F Joseph ^e   Littleton, Neil ^f   Wells, Richard A ^g   Sokol, Lubomir ^a   Wei, Sheng ^a   Komrokji, Rami S ^a   Boultwood, Jacqueline ^c   List, Alan F ^a   more..

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF SOUTH FLORIDA   (United States)

^c JOHN RADCLIFFE HOSPITAL   (United Kingdom)

^d Smith Holdings LLC   (United States)

^e Eleos Inc   (United States)

^f Provincial Hospital   (South Africa)

^g SUNNYBROOK RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CD34 ANTIGEN; CENERSEN; DEXAMETHASONE; LENALIDOMIDE; PROTEIN P53; PROTEIN S14; RIBOSOME PROTEIN; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; BONE MARROW SUPPRESSION; CELL EXPANSION; CELL ISOLATION; CELL PROLIFERATION; CHROMOSOME 5Q; CHROMOSOME DELETION 5; CONTROLLED STUDY; ERYTHROBLAST; ERYTHROID PRECURSOR CELL; ERYTHROPOIESIS; EXON; HUMAN; HUMAN CELL; IN VIVO STUDY; MYELODYSPLASTIC SYNDROME; PRIORITY JOURNAL; PROTEIN EXPRESSION;

BASE SEQUENCE; DEXAMETHASONE; DRUG RESISTANCE; ERYTHROID PRECURSOR CELLS; ERYTHROPOIESIS; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION, FLUORESCENCE; MOLECULAR SEQUENCE DATA; MYELODYSPLASTIC SYNDROMES; OLIGONUCLEOTIDES; REAL-TIME POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS, DNA; STATISTICS, NONPARAMETRIC; THALIDOMIDE; TREATMENT OUTCOME; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84885068819     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1311055110     Document Type: Article

References (26)

1. Nimer SD (2008) Myelodysplastic syndromes. Blood 111(10):4841-4851.
2. List A, et al.; Myelodysplastic Syndrome-003 Study Investigators (2006) Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl JMed 355(14):1456-1465.
3. Giagounidis AA, et al. (2004) Clinical, morphological, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31. Leukemia 18(1):113-119.
4. Giagounidis AA, Germing U, Aul C (2006) Biological and prognostic significance of chromosome 5q deletions in myeloid malignancies. Clin Cancer Res 12(1):5-10.
5. Boultwood J, et al. (2002) Narrowing and genomic annotation of the commonly deleted region of the 5q-syndrome. Blood 99(12):4638-4641.
6. Dutt S, et al. (2011) Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 117(9):2567-2576.
7. Lohrum MA, Ludwig RL, Kubbutat MH, Hanlon M, Vousden KH (2003) Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 3(6):577-587.
8. Barlow JL, et al. (2010) New insights into 5q-syndrome as a ribosomopathy. Cell Cycle 9(21):4286-4293.
9. List AF (2012) New therapeutics for myelodysplastic syndromes. Leuk Res 36(12): 1470-1474.
10. Wei S, et al. (2009) A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5qMDS by lenalidomide. Proc Natl Acad Sci USA 106(31):12974-12979.
11. Wei S, et al. (2013) Lenalidomide promotes p53 degradation by inhibiting MDM2 auto-ubiquitination in myelodysplastic syndrome with chromosome 5q deletion. Oncogene 32(9):1110-1120.
12. Dias N, Stein CA (2002) Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides. Eur J Pharm Biopharm 54(3):263-269.
13. Bennett CF, Swayze EE (2010) RNA targeting therapeutics: Molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 50:259-293.
14. Sharp JG, et al. (2001) Oligonucleotide enhanced cytotoxicity of Idarubicin for lymphoma cells. Leuk Lymphoma 42(3):417-427.
15. Bishop MR, et al. (1996) Phase I trial of an antisense oligonucleotide OL(1)p53 in hematologic malignancies. J Clin Oncol 14(4):1320-1326.
16. Cortes J, et al. (2012) Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia. Cancer 118(2):418-427.
17. Lanasa MC, et al. (2012) Phase II study of cenersen, an antisense inhibitor of p53, in combination with fludarabine, cyclophosphamide and rituximab for high-risk chronic lymphocytic leukemia. Leuk Lymphoma 53(2):218-224.
18. Ganguli G, Back J, Sengupta S, Wasylyk B (2002) The p53 tumour suppressor inhibits glucocorticoid-induced proliferation of erythroid progenitors. EMBO Rep 3(6):569-574.
19. Trainor CD, Mas C, Archambault P, Di Lello P, Omichinski JG (2009) GATA-1 associates with and inhibits p53. Blood 114(1):165-173.
20. Narla A, et al. (2011) Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis. Blood 118(8):2296-2304.
21. Leonova KI, et al. (2010) A small molecule inhibitor of p53 stimulates amplification of hematopoietic stem cells but does not promote tumor development in mice. Cell Cycle 9(7):1434-1443.
22. Jädersten M, et al. (2011) TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 29(15):1971-1979.
23. Kulasekararaj AG, et al. (2013) TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br J Haematol 160(5):660-672.
24. Bally CAL, et al. (2012) Incidence and Prognostic Value of TP53 Mutations in Lower Risk MDS with Del 5q. Blood 120:A1706.
25. Yip BH, et al. (2012) Effects of L-leucine in 5q-syndrome and other RPS14-deficient erythroblasts. Leukemia 26(9):2154-2158.
26. Cheson BD, et al. (2006) Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 108(2): 419-425.