A mechanistic pathogenetic model of myelodysplastic syndrome

David R Head


Myelodysplastic Syndrome (MDS) is a set of bone marrow failure diseases that remain difficult to diagnose, classify, and treat.  Some subtypes of MDS follow an aggressive course with short survival and a high rate of progression to a subset of acute myeloid leukemia (MDS-related or MDR-AML), while other subtypes have survival approaching that of age-matched peers, with infrequent or absent leukemic progression.  There is no effective model of MDS as a group,  of its subtypes, or of MDR-AML.  Current models do not satisfactorily address available data, and have led to no progress in diagnosis or treatment in over a decade.  A re-analysis of data on which these models is based leads to the conclusion that data may have been misinterpreted, with generation of faulty models of disease.  In this manuscript we review data on which the models are based, and generate an alternative interpretation of data and a new model of MDS.  This new model appears to correlate well with available data, leads to a modified classification of MDS, is testable, and if correct may lead to new approaches to diagnosis and treatment of MDS and MDR-AML.  This new model should be tested.


MDS; pathogenesis; AML


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