The stem cell fitness landscape and pathways of molecular leukemogenesis

Grover C. Bagby, Angela G. Fleischman

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

The relative risk of clonal evolution to either myelodysplasia (MDS) or acute myelogenous leukemia (AML) is high in patients with chronic bone marrow failure. From 10 to 20% of acquired aplastic anemia survivors will develop clonal evolution within the decade following their diagnosis as will 40% of patients with some of the inherited bone marrow failure syndromes. Studies on bone marrow failure states have provided some perspective on molecular pathogenesis of marrow failure and have also provided insights on the adaptive nature of clonal evolution. We review the scientific evidence validating this model, emphasize the importance of the fitness landscape in the stem cell pool, outline the clinical and investigative implications of the model, suggest that the lack of fitness in the starting pool accounts for the phenomenon of oncogene addiction, promote the value of the model for the evaluation of prevention strategies, and argue that experiments focusing attention on the relative phenotypes of neoplastic stem cell clones and pools of unfit stem cells from which they evolved will provide a useful paradigm of carcinogenesis in general.

Original languageEnglish (US)
Pages (from-to)487-500
Number of pages14
JournalFrontiers in Bioscience - Scholar
Volume3 S
Issue number2
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Keywords

  • Aplastic Anemia
  • Clonal Evolution
  • Fanconi Anemia
  • Hematopoietic Stem Cells
  • Interferon-Gamma
  • Leukemogenesis
  • Mutation
  • Myeloproliferative Diseases
  • Review
  • Tumor-Necrosis Factor-Alpha

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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