Abstract
Aplastic anemia is rare disorder presenting with bone marrow failure syndrome due to autoimmune destruction of early hematopoietic stem cells (HSCs) and stem cell progenitors. Recent advances in newer genomic sequencing and other molecular techniques have contributed to a better understanding of the pathogenesis of aplastic anemia with respect to the inflammaging, somatic mutations, cytogenetic abnormalities and defective telomerase functions of HSCs. These have been summarized in this review and may be helpful in differentiating aplastic anemia from hypocellular myelodysplastic syndrome. Furthermore, responses to immunosuppressive therapy and outcomes may be determined by molecular pathogenesis of HSCs autoimmune destruction, as well as treatment personalization in the future.
Highlights
Acquired aplastic anemia is a rare disorder presenting with bone marrow failure syndrome due to autoimmune destruction of early hematopoietic stem cells and stem cell progenitors [1, 2]
It was originally thought that AA was associated with damage to the haematopoiesis leading to the loss/destruction of hematopoietic stem cells (HSCs) by the following identifiable processes such as autoimmune mechanisms, direct damage to HSCs by drugs, chemicals or irradiation; virus infection and some inherited or acquired clonal and genetic disorders resulting in peripheral pancytopenia and a profound hypocellular bone marrow composed of fat cells and stroma [10]
Imi et al reported that in AA patients, hematopoietic stem progenitor cells (HSPCs) clones lacking an human leucocyte antigen (HLA) class I allele which escape the cytotoxic T lymphocyte (CTL) attack are essentially free from somatic mutations related to myeloid malignancies and are able to support long-term clonal hematopoiesis without developing driver mutations in AA patients unless HLA loss occurs in hematopoietic stem progenitor cells clones (HSPCs) with somatic mutations [47]
Summary
Acquired aplastic anemia is a rare disorder presenting with bone marrow failure syndrome due to autoimmune destruction of early hematopoietic stem cells and stem cell progenitors [1, 2]. Cases among males and females occur and most cases are observed in the first three decades of life. It was originally thought that AA was associated with damage to the haematopoiesis leading to the loss/destruction of hematopoietic stem cells (HSCs) by the following identifiable processes such as autoimmune mechanisms, direct damage to HSCs by drugs, chemicals or irradiation; virus infection and some inherited or acquired clonal and genetic disorders resulting in peripheral pancytopenia and a profound hypocellular bone marrow composed of fat cells and stroma [10]. There is evidence of a deficiency and/or dysfunction of T regulatory cells, this is impacted by class I and II HLA, NK cells and autoantibodies, which are involved in the immune destruction of HSCs in AA [20,21,22,23,24]
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