Oxymetholone therapy of fanconi anemia suppresses osteopontin transcription and induces hematopoietic stem cell cycling

Qing Shuo Zhang, Eric Benedetti, Matthew Deater, Kathryn Schubert, Angela Major, Carl Pelz, Soren Impey, Laura Marquez-Loza, R. Keaney Rathbun, Shigeaki Kato, Grover C. Bagby, Markus Grompe

Research output: Contribution to journalArticle

13 Scopus citations


Androgens are widely used for treating Fanconi anemia (FA) and other human bone marrow failure syndromes, but their mode of action remains incompletely understood. Aged Fancd2-/- mice were used to assess the therapeutic efficacy of oxymetholone (OXM) and its mechanism of action. Eighteen-month-old Fancd2-/- mice recapitulated key human FA phenotypes, including reduced bone marrow cellularity, red cell macrocytosis, and peripheral pancytopenia. As in humans, chronic OXM treatment significantly improved these hematological parameters and stimulated the proliferation of hematopoietic stem and progenitor cells. RNA-Seq analysis implicated downregulation of osteopontin as an important potential mechanism for the drug's action. Consistent with the increased stem cell proliferation, competitive repopulation assays demonstrated that chronic OXM therapy eventually resulted in stem cell exhaustion. These results expand our knowledge of the regulation of hematopoietic stem cell proliferation and have direct clinical implications for the treatment of bone marrow failure.

Original languageEnglish (US)
Pages (from-to)90-102
Number of pages13
JournalStem Cell Reports
Issue number1
StatePublished - Jan 13 2015


ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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