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Cytopenias: Acquired Bone Marrow Failure

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Diagnosis of Blood and Bone Marrow Disorders

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Abstract

Aplastic anemia (AA) is characterized by diminished or absent hematopoietic precursors in the bone marrow (BM), most often due to injury to the hematopoietic stem cell. AA can be congenital but is more frequently acquired. Acquired AA preferentially affects young adults (20–25 years) and individuals over the age of 55–60 years [1]. The incidence of acquired AA is estimated at two per million annually, and occurs at higher rates in countries with increased rates of viral hepatitis [2]. Table 4.1 lists the causative agents that have been reported associated with acquired AA. However, despite numerous, diverse possible causes, from chemicals and drugs to viral, collagen vascular diseases and pregnancy, in about 70% of patients, no clear cause can be determined and the AA is considered to be idiopathic [3]. It has been suggested that immune-mediated destruction/suppression may be the underlying cause in many of the patients with idiopathic AA. It has been postulated that damage induced by chemicals, drugs, viruses, or antigens leads to lymphocyte activation resulting in destruction of BM hematopoietic cells [4]. Studies have shown that autoreactive T-lymphocytes from the BM of patients with AA can inhibit hematopoiesis when co-cultured with normal marrows [5, 6]. This inhibition may be mediated by the release of marrow-suppressing cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor (TNF), and interleukin-2 [1], ultimately leading to apoptotic death of BM hematopoietic stem cells. IFN-γ may also lead to increased expression of the Fas and Fas receptor [7]. Telomeric attrition resulting in critically shortened telomeres, prompting cellular senescence or crisis, has also been considered one of the underlying causes of AA. Inherited heterozygous mutations in the genes that repair or protect telomere may limit marrow stem cell self-renewal and predispose some patients to marrow failure [8, 9].

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Authors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sa A. Wang M.D.

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  1. Sa A. Wang M.D.
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Correspondence to Sa A. Wang M.D. .

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Editors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sa A. Wang

  2. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    Robert P. Hasserjian

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Wang, S.A. (2018). Cytopenias: Acquired Bone Marrow Failure. In: Wang, S., Hasserjian, R. (eds) Diagnosis of Blood and Bone Marrow Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-20279-2_4

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  • DOI: https://doi.org/10.1007/978-3-319-20279-2_4

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