The fractal dimension of nuclear chromatin as a prognostic factor in acute precursor B lymphoblastic leukemia.

  • Adam R
  • Silva R
  • Pereira F
 et al. 
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The fractal nature of the DNA arrangement has been postulated to be a common feature of all cell nuclei. We investigated the prognostic importance of the fractal dimension (FD) of chromatin in blasts of patients with acute precursor B lymphoblastic leukemia (B-ALL). In 28 patients, gray scale transformed pseudo-3D images of 100 nuclei (May-Grünwald-Giemsa stained bone marrow smears) were analyzed. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R2 values in the log-log plots. Whereas FD presented no prognostic relevance, patients with higher R2 values showed a prolonged survival. White blood cell count (WBC), age and mean fluorescence intensity of CD45 (MFICD45) were all unfavorable prognostic factors in univariate analyses. In a multivariate Cox-regression, R2, WBC, and MFICD45, entered the final model, which showed to be stable in a bootstrap resampling study. Blasts with lower R2 values, equivalent to accentuated "coarseness" of the chromatin pattern, which may reflect profound changes of the DNA methylation, indicated a poor prognosis. In conclusion the goodness-of-fit of the Minkowski-Bouligand dimension of chromatin can be regarded as a new and biologically relevant prognostic factor for patients with B-ALL.

Author-supplied keywords

  • Azure Stains
  • Burkitt Lymphoma
  • Burkitt Lymphoma: diagnosis
  • Burkitt Lymphoma: pathology
  • Cell Nucleus
  • Cell Nucleus: pathology
  • Chromatin
  • Chromatin: pathology
  • DNA Methylation
  • Fractals
  • Humans
  • Prognosis
  • Proportional Hazards Models

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  • Randall L Adam

  • Rosana C Silva

  • Fernanda G Pereira

  • Neucimar J Leite

  • Irene Lorand-Metze

  • Konradin Metze

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