Abstract
We have investigated whether the p53 oncogene is expressed in the blast cells of patients with acute myeloblastic leukemia. p53 protein was detected in the blast cells of 19 out of 34 patients, but not in normal myelopoietic cells. We find a highly significant correlation between p53 protein synthesis in leukemic blast cells and the secondary plating efficiency of these cells (p = 0.0001). The latter provides an estimate for the self renewal capacity of progenitor cells in the blast population. These data indicate that p53 may be involved in leukemic stem cell renewal.
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Selected References
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- Benchimol S., Pim D., Crawford L. Radioimmunoassay of the cellular protein p53 in mouse and human cell lines. EMBO J. 1982;1(9):1055–1062. doi: 10.1002/j.1460-2075.1982.tb01296.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buick R. N., Minden M. D., McCulloch E. A. Self-renewal in culture of proliferative blast progenitor cells in acute myeloblastic leukemia. Blood. 1979 Jul;54(1):95–104. [PubMed] [Google Scholar]
- Buick R. N., Pollak M. N. Perspectives on clonogenic tumor cells, stem cells, and oncogenes. Cancer Res. 1984 Nov;44(11):4909–4918. [PubMed] [Google Scholar]
- Buick R. N., Till J. E., McCulloch E. A. Colony assay for proliferative blast cells circulating in myeloblastic leukaemia. Lancet. 1977 Apr 16;1(8016):862–863. doi: 10.1016/s0140-6736(77)92818-5. [DOI] [PubMed] [Google Scholar]
- Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
- Cheng G. Y., Curtis J. E., Tritchler D., McCulloch E. A. Response to hydrocortisone of blast progenitors in acute myeloblastic leukemia: an aspect of lineage infidelity. Leuk Res. 1985;9(12):1547–1557. doi: 10.1016/0145-2126(85)90048-7. [DOI] [PubMed] [Google Scholar]
- Crawford L. V., Pim D. C., Bulbrook R. D. Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer. 1982 Oct 15;30(4):403–408. doi: 10.1002/ijc.2910300404. [DOI] [PubMed] [Google Scholar]
- Crawford L. V., Pim D. C., Gurney E. G., Goodfellow P., Taylor-Papadimitriou J. Detection of a common feature in several human tumor cell lines--a 53,000-dalton protein. Proc Natl Acad Sci U S A. 1981 Jan;78(1):41–45. doi: 10.1073/pnas.78.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crawford L. V., Pim D. C., Lamb P. The cellular protein p53 in human tumours. Mol Biol Med. 1984 Aug;2(4):261–272. [PubMed] [Google Scholar]
- Crawford L., Leppard K., Lane D., Harlow E. Cellular proteins reactive with monoclonal antibodies directed against simian virus 40 T-antigen. J Virol. 1982 May;42(2):612–620. doi: 10.1128/jvi.42.2.612-620.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crawford L. The 53,000-dalton cellular protein and its role in transformation. Int Rev Exp Pathol. 1983;25:1–50. [PubMed] [Google Scholar]
- Eliyahu D., Michalovitz D., Oren M. Overproduction of p53 antigen makes established cells highly tumorigenic. Nature. 1985 Jul 11;316(6024):158–160. doi: 10.1038/316158a0. [DOI] [PubMed] [Google Scholar]
- Eliyahu D., Raz A., Gruss P., Givol D., Oren M. Participation of p53 cellular tumour antigen in transformation of normal embryonic cells. Nature. 1984 Dec 13;312(5995):646–649. doi: 10.1038/312646a0. [DOI] [PubMed] [Google Scholar]
- Fialkow P. J., Singer J. W., Adamson J. W., Vaidya K., Dow L. W., Ochs J., Moohr J. W. Acute nonlymphocytic leukemia: heterogeneity of stem cell origin. Blood. 1981 Jun;57(6):1068–1073. [PubMed] [Google Scholar]
- Greaves M. F., Chan L. C., Furley A. J., Watt S. M., Molgaard H. V. Lineage promiscuity in hemopoietic differentiation and leukemia. Blood. 1986 Jan;67(1):1–11. [PubMed] [Google Scholar]
- Harlow E., Crawford L. V., Pim D. C., Williamson N. M. Monoclonal antibodies specific for simian virus 40 tumor antigens. J Virol. 1981 Sep;39(3):861–869. doi: 10.1128/jvi.39.3.861-869.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoang T., McCulloch E. A. Production of leukemic blast growth factor by a human bladder carcinoma cell line. Blood. 1985 Sep;66(3):748–751. [PubMed] [Google Scholar]
- Matlashewski G., Banks L., Pim D., Crawford L. Analysis of human p53 proteins and mRNA levels in normal and transformed cells. Eur J Biochem. 1986 Feb 3;154(3):665–672. doi: 10.1111/j.1432-1033.1986.tb09449.x. [DOI] [PubMed] [Google Scholar]
- Matlashewski G., Lamb P., Pim D., Peacock J., Crawford L., Benchimol S. Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene. EMBO J. 1984 Dec 20;3(13):3257–3262. doi: 10.1002/j.1460-2075.1984.tb02287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCulloch E. A., Curtis J. E., Messner H. A., Senn J. S., Germanson T. P. The contribution of blast cell properties to outcome variation in acute myeloblastic leukemia (AML). Blood. 1982 Mar;59(3):601–608. [PubMed] [Google Scholar]
- Mercer W. E., Baserga R. Expression of the p53 protein during the cell cycle of human peripheral blood lymphocytes. Exp Cell Res. 1985 Sep;160(1):31–46. doi: 10.1016/0014-4827(85)90233-2. [DOI] [PubMed] [Google Scholar]
- Milner J. Different forms of p53 detected by monoclonal antibodies in non-dividing and dividing lymphocytes. Nature. 1984 Jul 12;310(5973):143–145. doi: 10.1038/310143a0. [DOI] [PubMed] [Google Scholar]
- Milner J., Milner S. SV40-53K antigen: a possible role for 53K in normal cells. Virology. 1981 Jul 30;112(2):785–788. doi: 10.1016/0042-6822(81)90327-5. [DOI] [PubMed] [Google Scholar]
- Minden M. D., Buick R. N., McCulloch E. A. Separation of blast cell and T-lymphocyte progenitors in the blood of patients with acute myeloblastic leukemia. Blood. 1979 Jul;54(1):186–195. [PubMed] [Google Scholar]
- Mowat M., Cheng A., Kimura N., Bernstein A., Benchimol S. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature. 1985 Apr 18;314(6012):633–636. doi: 10.1038/314633a0. [DOI] [PubMed] [Google Scholar]
- Oren M., Maltzman W., Levine A. J. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. doi: 10.1128/mcb.1.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oren M. The p53 cellular tumor antigen: gene structure, expression and protein properties. Biochim Biophys Acta. 1985 Nov 12;823(1):67–78. doi: 10.1016/0304-419x(85)90015-0. [DOI] [PubMed] [Google Scholar]
- Parada L. F., Land H., Weinberg R. A., Wolf D., Rotter V. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature. 1984 Dec 13;312(5995):649–651. doi: 10.1038/312649a0. [DOI] [PubMed] [Google Scholar]
- Reich N. C., Levine A. J. Growth regulation of a cellular tumour antigen, p53, in nontransformed cells. Nature. 1984 Mar 8;308(5955):199–201. doi: 10.1038/308199a0. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Thomas R., Kaplan L., Reich N., Lane D. P., Levine A. J. Characterization of human p53 antigens employing primate specific monoclonal antibodies. Virology. 1983 Dec;131(2):502–517. doi: 10.1016/0042-6822(83)90516-0. [DOI] [PubMed] [Google Scholar]
- Till J. E., McCulloch E. A. Hemopoietic stem cell differentiation. Biochim Biophys Acta. 1980 Nov 26;605(4):431–459. doi: 10.1016/0304-419x(80)90009-8. [DOI] [PubMed] [Google Scholar]
- Wade-Evans A., Jenkins J. R. Precise epitope mapping of the murine transformation-associated protein, p53. EMBO J. 1985 Mar;4(3):699–706. doi: 10.1002/j.1460-2075.1985.tb03686.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiggans R. G., Jacobson R. J., Fialkow P. J., Woolley P. V., 3rd, Macdonald J. S., Schein P. S. Probable clonal origin of acute myeloblastic leukemia following radiation and chemotherapy of colon cancer. Blood. 1978 Oct;52(4):659–663. [PubMed] [Google Scholar]
- Wolf D., Harris N., Goldfinger N., Rotter V. Isolation of a full-length mouse cDNA clone coding for an immunologically distinct p53 molecule. Mol Cell Biol. 1985 Jan;5(1):127–132. doi: 10.1128/mcb.5.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolf D., Harris N., Rotter V. Reconstitution of p53 expression in a nonproducer Ab-MuLV-transformed cell line by transfection of a functional p53 gene. Cell. 1984 Aug;38(1):119–126. doi: 10.1016/0092-8674(84)90532-4. [DOI] [PubMed] [Google Scholar]
- Wolf D., Rotter V. Inactivation of p53 gene expression by an insertion of Moloney murine leukemia virus-like DNA sequences. Mol Cell Biol. 1984 Jul;4(7):1402–1410. doi: 10.1128/mcb.4.7.1402. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolf D., Rotter V. Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells. Proc Natl Acad Sci U S A. 1985 Feb;82(3):790–794. doi: 10.1073/pnas.82.3.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
