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

  • L. Wolff
  • R. Koller
  • J. Bies
  • V. Nazarov
  • B. Hoffman
  • A. Amanullah
  • M. Krall
  • B. Mock
Part of the Current Topics in Microbiology and Immunology book series (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.

Keywords

Lymphoma Leukemia Carboxyl Electrophoresis Peritoneal Inflammation 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • L. Wolff
    • 1
  • R. Koller
    • 1
  • J. Bies
    • 1
  • V. Nazarov
    • 1
  • B. Hoffman
    • 1
  • A. Amanullah
    • 1
  • M. Krall
    • 1
  • B. Mock
    • 2
  1. 1.Laboratory of GeneticsNational Cancer InstituteBethesdaUSA
  2. 2.Fels Institute for Cancer Research and Molecular BiologyTemple University School of MedicinePhiladelphiaUSA

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