Molecular Targets in Myelodysplastic Syndromes

Abstract

Myelodysplastic syndromes are characterized by peripheral cytopenias in combination with a hyperplastic bone marrow. The classification according to the WHO includes mainly morphological criteria and is supplemented by the International Prognostic Scoring System which takes cytogenetical changes into consideration when determining the prognosis of MDS. The underlying mechanisms causing primary MDS requires further work. Different molecular alterations which have been described, suggest that it is a multistep alteration to the haematopoietic stem cells that include genes involved in cell cycle control, mitotic checkpoints as well as growth factor receptors. Secondary signal proteins and transcription factors which gives the cell a growth advantage over its normal counterpart, may be affected as well. The accumulation of such defects may finally cause the leukaemic transformation of MDS. Myelodysplastic syndromes are characterized by peripheral cytopenias in combination with a hyperplastic bone marrow. The classification according to the WHO includes mainly morphological criteria and is supplemented by the International Prognostic Scoring System which takes cytogenetical changes into consideration when determining the prognosis of MDS. The underlying mechanisms causing primary MDS requires further work. Different molecular alterations which have been described, suggest that it is a multistep alteration to the haematopoietic stem cells that include genes involved in cell cycle control, mitotic checkpoints as well as growth factor receptors. Secondary signal proteins and transcription factors which gives the cell a growth advantage over its normal counterpart, may be affected as well. The accumulation of such defects may finally cause the leukaemic transformation of MDS.