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Retroviral Insertional Mutagenesis in Murine Promonocytic Leukemias:c-myb and Mm/1

  • Conference paper
Molecular Aspects of Myeloid Stem Cell Development

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 211))

Abstract

Studies have focused on two genetic loci, c-myb and Mml1, whose activation by retroviral insertional mutagenesis contribute to promonocytic leukemia in our acute monocytic leukemia (AMoL) model. Multiple mechanisms of activation of c-myb by retroviral insertional mutagenesis implicate both transcriptional deregulation and protein truncation in conversion of this proto-oncogene to an oncogene. Because transformation by c-Myb can be viewed as a block to differentiation our studies moved into two in vitro systems to evaluate effects of truncated forms of c-Myb on cytokine induced maturation of myeloid progenitors to the granulocyte and macrophage lineages. Deregulated expression of truncated and full length c-Myb did not result in maintenance of the myelomonocytic progenitor state but rather a block in differentiation at intermediate to late steps in the maturation processes of myelomonocytic cells. Our results argue that inhibition of differentiation is due to c-Myb’s ability to maintain the proliferative state of cells. Interestingly, the phenotype of continuously proliferating monocytic cells resembles that of the tumor cell phenotype. Recently we identified a new target of integration, Mml1, which is rearranged in ten promonocytic leukemias that do not have c-myb rearrangements. This locus which was mapped to chromosome 10 is presently being characterized.

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Author information

Authors and Affiliations

  1. Laboratory of Genetics, National Cancer Institute, Bethesda, MD, 20892-4255, USA

    L. Wolff, R. Koller, J. Bies, V. Nazarov, B. Hoffman, A. Amanullah & M. Krall

  2. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    B. Mock

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  1. L. Wolff
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  2. R. Koller
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  3. J. Bies
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  4. V. Nazarov
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  5. B. Hoffman
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  6. A. Amanullah
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  7. M. Krall
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Editor information

Editors and Affiliations

  1. Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bldg. 37, Rm. 1 B16, 37 Convent Drive MSC 4255, Bethesda, MD, 20892-4255, USA

    Linda Wolff Ph.D. (Senior Investigator) (Senior Investigator)

  2. Department of Pathology, Yale University School of Medicine, P.O. Box 208023, New Haven, CT, 06520-8023, USA

    Archibald S. Perkins M.D., Ph.D. (Assistant Professor) (Assistant Professor)

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© 1996 Springer-Verlag Berlin Heidelberg

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Wolff, L. et al. (1996). Retroviral Insertional Mutagenesis in Murine Promonocytic Leukemias:c-myb and Mm/1. In: Wolff, L., Perkins, A.S. (eds) Molecular Aspects of Myeloid Stem Cell Development. Current Topics in Microbiology and Immunology, vol 211. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85232-9_19

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  • DOI: https://doi.org/10.1007/978-3-642-85232-9_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-85234-3

  • Online ISBN: 978-3-642-85232-9

  • eBook Packages: Springer Book Archive

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