An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in fanconi anemia

Yuan Zhou, Yongzheng He, Wen Xing, Peng Zhang, Hui Shi, Shi Chen, Jun Shi, Jie Bai, Steven D. Rhodes, Fengqui Zhang, Jin Yuan, Xianlin Yang, Xiaofan Zhu, Yan Li, Helmut Hanenberg, Mingjiang Xu, Kent A. Robertson, Weiping Yuan, Grzegorz Nalepa, Tao ChengD. Wade Clapp, Feng-Chun Yang

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation.

Original languageEnglish (US)
Pages (from-to)1017-1027
Number of pages11
JournalHaematologica
Volume102
Issue number6
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • Hematology

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  • Cite this

    Zhou, Y., He, Y., Xing, W., Zhang, P., Shi, H., Chen, S., Shi, J., Bai, J., Rhodes, S. D., Zhang, F., Yuan, J., Yang, X., Zhu, X., Li, Y., Hanenberg, H., Xu, M., Robertson, K. A., Yuan, W., Nalepa, G., ... Yang, F-C. (2017). An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in fanconi anemia. Haematologica, 102(6), 1017-1027. https://doi.org/10.3324/haematol.2016.158717