Clonal Analysis of n-ras Gene Activation in Acute Myeloid Leukemia

  • M. Lübbert
  • W. Oster
  • F. McCormick
  • R. Mertelsmann
  • F. Herrmann
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 131)


Members of the ras gene family code for 21-kDa proteins (p21) located at the inner cellular membrane. Several lines of evidence suggest that p21 proteins are involved in intracellular signal transduction pathways, thus regulating cellular growth and differentiation. Ras proteins bind and hydrolyze GTP (Gibbs et al. 1984; Sweet et al. 1984) and show sequence homology to G proteins (Hurley et al. 1984) which are thought to participate in the action of some cytokines. The p21 of n-ras has been shown to couple receptor binding of hematopoietic growth factors to inositol lipid hydrolysis in fibroblasts (Wakelam et al. 1986). Conversely, activation of G proteins by sodium fluoride in the presence of Al3+ results in expression of cytokines (Yamato et al. 1989), and expression of an activated ras gene transfected into normal cells or cell lines can induce cytokine expression by these cells (Yiagnisis and Spandidos 1987; Demetri et al. 1988; Andrejauskas and Moroni 1989) and change their responsiveness towards growth factors (Kelekar and Cole 1987; Leof et al. 1987). Point mutations leading to an activated p21 occur in numerous human malignancies (for a review, see Bos 1988). Activating mutations of n-ras have been reported to occur in 25%–40% of cases of acute myelogenous leukemia (AML). (Bos et al. 1985; Janssen et al. 1987; Farr et al. 1988). However, the presence of these mutations can be restricted to subpopulations (subclones) of leukemic cells (Toksoz et al. 1987).


Acute Myeloid Leukemia Acute Myelogenous Leukemia Clonal Analysis Activate Point Mutation Soft Agar Culture 
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Copyright information

© Springer-Verlag Berlin · Heidelberg 1993

Authors and Affiliations

  • M. Lübbert
    • 1
  • W. Oster
    • 2
  • F. McCormick
    • 3
  • R. Mertelsmann
    • 1
  • F. Herrmann
    • 4
  1. 1.Department of Internal Medicine 1University of Freiburg Medical CenterFreiburgFed. Rep. of Germany
  2. 2.Behringwerke AGMarburgFed. Rep. of Germany
  3. 3.Cetus CorporationEmeryvilleUSA
  4. 4.Department of Medical Oncology and Applied Molecular Biology, UKRVFree University of BerlinBerlinGermany

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