alexa Pathogenesis, etiology and epidemiology of myelodysplastic syndromes.
Clinical Research

Clinical Research

Journal of Clinical Case Reports

Author(s): Aul C, Bowen DT, Yoshida Y

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Abstract BACKGROUND AND OBJECTIVE: The myelodysplastic syndromes are common hematological malignancies affecting predominantly elderly people. Patients usually present with chronic cytopenias which gradually worsen due to progressive bone marrow failure or transformation into acute myeloid leukemia. Disease prevention is more cost-effective than therapeutic intervention and the establishment of the etiology and pathogenesis of MDS therefore assumes considerable importance. This review will outline current concepts of the pathobiology of MDS, putative etiological insults and the mechanisms of disease initiation as well as recent contributions to the descriptive epidemiology of these disorders. EVIDENCE AND INFORMATION SOURCES: The authors of the present review have a long-standing interest in the pathogenesis, etiology and epidemiology of MDS. Journal articles covered by the Science Citation Index and Medline have been reviewed and personal experience and discussion with international experts collated. STATE OF THE ART AND PERSPECTIVES: The initiation processes for the development of MDS remain unknown. A poorly defined transforming event affects a pluripotent or multipotent progenitor cell in the bone marrow, conferring a growth advantage upon it and eventually establishing clonal hematopoiesis. An important pathogenetic mechanism in MDS is premature intramedullary cell death via excessive apoptosis, explaining the apparent paradox of a cellular marrow in combination with peripheral cytopenias (ineffective hematopoiesis). Therapy-related MDS/AML following exposure to alkylating agents is the only clear etiological factor thus identified. Increasing evidence for exposure to benzene and radiation and the development of MDS is emerging. Benzene hematotoxicity is mediated via both genotoxic and non-genotoxic mechanisms, leading to aplasia, apoptosis and initiation (via genetic mutation) of clonal disorders such as MDS. Further studies of benzene hematotoxicity and therapy-related MDS should provide models for the elucidation of initiation events in MDS pathogenesis. The importance of such studies is emphasized by the rising frequency of MDS which largely reflects improved diagnostic criteria, increased physician awareness and extended use of diagnostic procedures in the elderly. Demographic changes will lead to a marked increase in MDS over the next few decades.
This article was published in Haematologica and referenced in Journal of Clinical Case Reports

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