A small molecule inhibitor of p53 stimulates amplification of hematopoietic stem cells but does not promote tumor development in mice

Cell Cycle

Volumn 9, Issue 7, 2010, Pages 1434-1443

  Leonova, Katerina I ^a   Shneyder, Jelena ^a   Antoch, Marina P ^a   Toshkov, Illia A ^b   Novototskaya, Liliya R ^a   Komarov, Pavel G ^b   Komarova, Elena A ^a   Gudkov, Andrei V ^a,b  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

^b CLEVELAND BIOLABS INC   (United States)

Author keywords

Cancer; Hematopoietic stem cells; Lymphoma; p53 inhibitor; Radiation; Sarcoma

Indexed keywords

ANTINEOPLASTIC AGENT; PIFITHRIN BETA; PROTEIN P53; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD; BONE MARROW CELL; CARCINOGENESIS; CARCINOGENICITY; CELL POPULATION; CELL PROLIFERATION; CELL SIZE; CONTROLLED STUDY; FLOW CYTOMETRY; GAMMA IRRADIATION; HEMATOPOIETIC STEM CELL; MOUSE; NONHUMAN; RADIATION PROTECTION;

MUS;

EID: 77953578553     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.9.7.11508     Document Type: Article

References (33)

1. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992; 356:215-21.
2. Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT, Weinberg RA. Tumor spectrum analysis in p53-mutant mice. Curr Biol 1994; 4:1-7.
3. Varley JM, McGown G, Thorncroft M, Santibanez-Koref MF, Kelsey AM, Tricker KJ, et al. Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res 1997; 57:3245-52.
4. Liu Y, Elf SE, Miyata Y, Sashida G, Liu Y, Huang G, et al. p53 regulates hematopoietic stem cell quiescence. Cell stem cell 2009; 4:37-48.
5. Krizhanovsky V, Lowe SW. Stem cells: The promises and perils of p53. Nature 2009; 460:1085-6.
6. Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature 1991; 351:453-6.
7. Hong H, Takahashi K, Ichisaka T, Aoi T, Kanagawa O, Nakagawa M, et al. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 2009; 460:1132-5.
8. Li H, Collado M, Villasante A, Strati K, Ortega S, Canamero M, et al. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 2009; 460:1136-9.
9. Kawamura T, Suzuki J, Wang YV, Menendez S, Morera LB, Raya A, et al. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 2009; 460:1140-4.
10. Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, et al. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 2009; 460:1145-8.
11. Marion RM, Strati K, Li H, Murga M, Blanco R, Ortega S, et al. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 2009; 460:1149-53.
12. Meletis K, Wirta V, Hede SM, Nister M, Lundeberg J, Frisen J. p53 suppresses the self-renewal of adult neural stem cells. Development 2006; 133:363-9.
13. Arf-/- multipotent progenitors. Nature 2008; 453:228-32.
14. Dumble M, Moore L, Chambers SM, Geiger H, Van Zant G, Goodell MA, Donehower LA. The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood 2007; 109:1736-42. (Pubitemid 46239609)
15. TeKippe M, Harrison DE, Chen J. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 2003; 31:521-7. (Pubitemid 36793959)
16. Chen J, Ellison FM, Keyvanfar K, Omokaro SO, Desierto MJ, Eckhaus MA, Young NS. Enrichment of hematopoietic stem cells with SLAM and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null mice. Exp Hematol 2008; 36:1236-43.
17. Komarova EA, Gudkov AV. Could p53 be a target for therapeutic suppression? Semin Cancer Biol 1998; 8:389-400.
18. Gudkov AV, Komarova EA. Prospective therapeutic applications of p53 inhibitors. Biochem Biophys Res Commun 2005; 331:726-36.
19. Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, Gudkov AV. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 1999; 285:1733-7. (Pubitemid 29428873)
20. Wang Y, Schulte BA, LaRue AC, Ogawa M, Zhou D. Total body irradiation selectively induces murine hematopoietic stem cell senescence. Blood 2006; 107:358-66. (Pubitemid 43053564)
21. French J, Storer RD, Donehower LA. The nature of the heterozygous Trp53 knockout model for identification of mutagenic carcinogens. Toxicol Pathol 2001; 29:24-9. (Pubitemid 33026792)
22. Kemp CJ, Wheldon T, Balmain A. p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis. Nat Genet 1994; 8:66-9. (Pubitemid 24274062)
23. Komarova EA, Kondratov RV, Wang K, Christov K, Golovkina TV, Goldblum JR, Gudkov AV. Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice. Oncogene 2004; 23:3265-71. (Pubitemid 38669816)
24. Spangrude GJ, Aihara Y, Weissman IL, Klein J. The stem cell antigens Sca-1 and Sca-2 subdivide thymic and peripheral T lymphocytes into unique subsets. J Immunol 1988; 141:3697-707.
25. Osawa M, Hanada K, Hamada H, Nakauchi H. Longterm lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science (New York, NY) 1996; 273:242-5.
26. Spangrude GJ, Brooks DM. Mouse strain variability in the expression of the hematopoietic stem cell antigen Ly-6A/E by bone marrow cells. Blood 1993; 82:3327-32.
27. van de Rijn M, Heimfeld S, Spangrude GJ, Weissman IL. Mouse hematopoietic stem-cell antigen Sca-1 is a member of the Ly-6 antigen family. Proc Natl Acad Sci USA 1989; 86:4634-8.
28. Filshie RJ. Cytokines in haemopoietic progenitor mobilisation for peripheral blood stem cell transplantation. Curr Pharm Des 2002; 8:379-94.
29. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 1996; 183:1797-806.
30. Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004; 118:149-61.
31. Lowe SW, Cepero E, Evan G. Intrinsic tumour suppression. Nature 2004; 432:307-15.
32. Mitchel RE, Jackson JS, Morrison DP, Carlisle SM. Low doses of radiation increase the latency of spontaneous lymphomas and spinal osteosarcomas in cancerprone, radiation-sensitive Trp53 heterozygous mice. Radiat Res 2003; 159:320-7.
33. Christophorou MA, Ringshausen I, Finch AJ, Swigart LB, Evan GI. The pathological response to DNA damage does not contribute to p53-mediated tumour suppression. Nature 2006; 443:214-7.