Approach to the molecular mechanisms of hematopoietic dysplasia aiming at elucidation of the pathogenesis of myelodysplastic syndromes

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I focused attention on vimentin, one of the intermediate filaments which support cell shape and might be involved in the mechanisms of hematopoietic dysplasia, and examined the change of vimentin expression during the differentiation process of human leukemic HL60 cell line. Vimentin expression was down-regulated in the process of neutrophil-like differentiation of HL60 cells, while it was extremely up-regulated in the process of macrophage-like differentiation.Next, I established HL60 cell clones whose vimentin expression was knock-downed by transfer of a lentiviral vector harboring vimentin-shRNA. Such vimentin-knock-downed clones were induced to differentiation and revealed increased leukocyte activity such as cell movement and phagocytosis. These data suggested that vimentin regulates leukocyte function negatively.