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New therapeutic approaches for protecting hematopoietic stem cells in aplastic anemia

  • Immunology & Microbiology in Miami
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Abstract

Aplastic anemia (AA) is an immune-mediated and life-threatening form of acquired bone marrow failure (BMF), characterized by development and expansion of self-reactive T cells. These T cells cause continuous destruction of hematopoietic stem cells (HSCs), progenitors, and mature blood cells, leading to severe and if left untreated fatal marrow hypoplasia and pancytopenia. Standard treatment options for patients with AA include: (1) immunosuppressive therapy (IST) with anti-thymocyte globulin and cyclosporine A which targets self-reactive T cells, or (2) matched sibling or unrelated BM transplant (BMT). The IST treatment is often not effective due to poor response to therapy or disease relapse after IST. Also, BMT is not an option for many patients due to their age, comorbidities, and the lack of histocompatible donor. This necessitates development and testing of novel approaches to reduce severity of AA and to efficiently treat patients with refractory and relapsed AA. Immune-mediated AA was reproduced in animals, including mouse lymphocyte infusion models, which are used to study further etiology and pathophysiology of AA and test new drugs and approaches in treating and managing AA. In these mouse models the immune correlates and pathologic features of AA are strikingly similar to features of severe human AA. In this article we (a) briefly review standard and developing approaches for treating AA and (b) describe development and testing of novel treatment approach with a potential to safely reduce BM hypoplasia and significantly decrease the loss of HSCs in mouse lymphocyte infusion model of AA.

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Acknowledgments

This work is supported by UMMSM Interdisciplinary Team Science Pilot Program Grant (to R.J.).

Conflict of interest

W.W., R.A., and R.J. have no conflict of interest. V.G. is an inventor of pending patents related to Leukadherins and has the potential for financial benefit from their future commercialization.

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  1. Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA

    Wendy Weston, Rebecca Adkins & Roland Jurecic

  2. Department of Medicine, Rush University Medical Center, Chicago, IL, USA

    Vineet Gupta

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  1. Wendy Weston
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Correspondence to Roland Jurecic.

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Weston, W., Gupta, V., Adkins, R. et al. New therapeutic approaches for protecting hematopoietic stem cells in aplastic anemia. Immunol Res 57, 34–43 (2013). https://doi.org/10.1007/s12026-013-8449-0

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