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Lack of p53 expression in human myeloid leukemias is not due to mutations in transcriptional regulatory regions of the gene

Leukemia volume 16, pages 2165–2167 (2002)Cite this article

The normal or wild-type p53 gene encodes a DNA-binding transcription factor that is responsible for cell cycle checkpoints that are activated after exposure to DNA damaging agents.1 A hallmark of many tumor cells is that the p53 gene is mutated and expressed at greatly elevated levels. We have been interested in determining the cause of lack of expression of the p53 gene in cell lines derived from myeloid leukemias. Although numerous tumor types express elevated levels of mutant p53, it has been demonstrated that some astrocytomas,2 a high proportion of breast cancers3 and many human myeloid leukemias do not express detectable levels of p53 mRNA.4 The mechanism responsible for the silencing of p53 expression in myeloid tumors remains unknown. The loss of p53 gene expression in these cells is likely to be an important step in cancer progression and could result from cis-acting mutations within the regulatory regions of the gene or from the loss of required trans-acting factors. Our goal has been to determine whether mutational events in the p53 transcriptional regulatory regions of the gene represent a mechanism by which p53 expression is silenced.

There are a number of possible explanations for the lack of expression of p53 in myeloid lines. One explanation, found to be the case in HL-60 cells, is that loss of expression is due to deletions in the gene.4 In order to test this possibility we performed Southern transfer analysis to assay for the presence of an intact human p53 transcriptional regulatory region and for the presence of intact p53 coding sequences. Within the limits of resolution of these assays, the cells appear to carry an intact p53 gene and intact upstream sequences with no detectable deletions or rearrangements. Therefore, the loss of p53 expression is not due to the loss of or to major rearrangements in the gene or its regulatory sequences.

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Acknowledgements

The authors thank Nicole Doudican and Marna Hill for technical support and Kristy Boggs for discussions. Funding was from the NIH.

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  1. Eli Lilly and Company, Indianapolis, IN, USA

    S Durland-Busbice

  2. Department of Biological Sciences, University of South Carolina, Columbia, SC, USA

    D Reisman

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  1. S Durland-Busbice
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Durland-Busbice, S., Reisman, D. Lack of p53 expression in human myeloid leukemias is not due to mutations in transcriptional regulatory regions of the gene. Leukemia 16, 2165–2167 (2002). https://doi.org/10.1038/sj.leu.2402647

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