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Anemia
Volume 2012, Article ID 265790, 18 pages
http://dx.doi.org/10.1155/2012/265790
Review Article

Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

1Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Experimental Hematology 69120, Heidelberg, Germany
2Experimental Hematology Group, Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, 69120 Heidelberg, Germany

Received 9 January 2012; Accepted 13 March 2012

Academic Editor: Laura Hays

Copyright © 2012 Anja Geiselhart et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients.