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Pathogenesis of Clonal Dominance in PNH: Selection Mechanisms in PNH

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Paroxysmal Nocturnal Hemoglobinuria

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Abstract

It appears that the presence of a mutation of the PIGA gene alone is not sufficient for the development of paroxysmal nocturnal hemoglobinuria (PNH) and that concomitant expansion of PIGA-mutant clones is indispensable; however, the mechanism of such expansion is not yet fully elucidated. Because of the close association between idiopathic aplastic anemia and PNH, the prevailing hypothesis is that PNH progenitor cells can survive rather than normal progenitor cells against autoimmune attack on bone marrow cells by evading immune recognition with the aid of their membrane characteristics, leading to selective expansion of PNH clones. Various attempts have so far been made to prove this hypothesis, including examining the apoptosis resistance of PNH hematopoietic cells, involvement of conventional cytotoxic T cells or certain T-cell subsets such as CD1d-restricted T cells and natural killer receptor-expressing T cells as the immune effector cells, and involvement of natural killer cells under some stress situations. In this chapter, the results of these studies will be outlined; we will also refer to our own findings on the relationship between NKG2D-mediated immunity and the clonal selection of PNH cells.

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Authors and Affiliations

  1. Departments of Hematology & Infectious Diseases, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuoku, 860-8556, Kumamoto, Japan

    Tatsuya Kawaguchi M.D., Ph.D.

  2. Kagoshima-Tokushukai Hospital, 3-8-1 Shimo-Arata, Kagoshima, 890-0056, Japan

    Hideki Nakakuma

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  1. Tatsuya Kawaguchi M.D., Ph.D.
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  2. Hideki Nakakuma
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Correspondence to Tatsuya Kawaguchi M.D., Ph.D. .

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Editors and Affiliations

  1. Department of Hematology and Ocology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Yuzuru Kanakura

  2. Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan

    Taroh Kinoshita

  3. Dept of Hematology and Ocology, Osaka University Dept of Hematology and Ocology, Suita, Osaka, Japan

    Jun-ichi Nishimura

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Kawaguchi, T., Nakakuma, H. (2017). Pathogenesis of Clonal Dominance in PNH: Selection Mechanisms in PNH. In: Kanakura, Y., Kinoshita, T., Nishimura, Ji. (eds) Paroxysmal Nocturnal Hemoglobinuria. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56003-6_13

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  • DOI: https://doi.org/10.1007/978-4-431-56003-6_13

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  • Online ISBN: 978-4-431-56003-6

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