Bone Marrow Failure Secondary to Cytokinesis Failure

Abstract

Fanconi anemia (FA) is a human genetic disease characterized by a progressive bone marrow failure and heightened susceptibility to cancer. The main objective of our project was to understand the mechanisms of bone marrow failure in FA. The specific objective was to determine the role of cytokinesis failure of hematopoietic stem cells in the pathogenesis of bone marrow failure in FA. During the award period, we have assessed the role of FA pathway in mitosis and confirmed that murine FA-deficient hematopoietic stem cells exhibit p53-mediated growth defects, cytokinesis failure and apoptosis. In order to study the role of bone marrow microenvironment in bone marrow failure in FA, we have also evaluated primary FA-deficient bone marrow stromal cells for mitotic defects. Interestingly, these cells also exhibit cytokinesis defects. Collectively, our results suggest that bone marrow failure in FA may be caused, in part, by p53-mediated cellular defects and underscore the importance of therapeutically targeting p53 in FA.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2015
Accession Number
AD1009088

Entities

People

  • Alan D'Andrea

Organizations

  • Dana–Farber Cancer Institute

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biomedical Research
  • Bone Marrow
  • Bone Marrow Cells
  • Bones
  • Cancer
  • Cell Division
  • Cell Physiological Processes
  • Cells
  • Contracts
  • Department Of Defense
  • Genetic Phenomena
  • Growth Factors
  • Hematopoietic Cells
  • Stem Cells
  • Stromal Cells

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology