Hypothesis: myelodysplastic syndromes may have a viral etiology.

An 'initial transforming event(s)' in a pluripotential bone marrow (BM) stem cell confers a growth advantage upon it leading to clonal expansion accompanied by dysplastic maturation resulting in myelodysplastic syndromes (MDS). The nature of this 'initial' event in MDS is obscure. We propose that MDS can begin as a viral disease. It may be a dormant lentivirus which is made oncogenic by 'promoting events' such as immunosuppression, or a second viral infection. The infected cell may not be a BM stem cell, but a cell belonging to the BM stroma or to the immune system. Dysregulated cytokine production as a consequence of the infection can change the BM microenvironment in such a way that optimal growth support is provided only to a rapidly proliferating stem cell. Karyotypically marked (or unmarked) abnormal stem cells may exist or arise frequently but do not thrive in a 'normal' cytokine milieu. However, with the changed BM landscape, these abnormal clones may enjoy a growth advantage leading to a monoclonal hypercellular BM and variable cytopenias. Circumstantial evidence to support the possibility that the initial transforming event in MDS is a viral insult is presented in this hypothesis paper.