Molecular mechanisms of the progression of myelodysplastic syndrome to secondary acute myeloid leukaemia and implication for therapy.

Myelodysplastic syndrome (MDS) includes a heterogeneous group of clonal haematological stem cell disorders characterized by dysplasia, cytopenias, ineffective haematopoiesis, and an increased risk of progression to acute myeloid leukaemia (AML), which is also called secondary AML (sAML). Approximately one-third of patients with MDS will progress to sAML within a few months to a few years, and this type of transformation is more common and rapid in patients with high-risk MDS (HR-MDS). However, the precise mechanisms underlying the evolution of MDS to sAML remain unclear. Currently, chemotherapy for sAML has minimal efficacy. The only method of curing patients with sAML is allogeneic haematopoietic stem cell transplantation (Allo-HSCT). Unfortunately, only a few patients are appropriate for transplantation because this disease primarily affects older adult patients. Additionally, compared to de novo AML, sAML is more difficult to cure, and the prognosis is often worse. Therefore, it is important to clarify the molecular mechanisms of the progression of MDS to sAML and to explore the potent drugs for clinical use. This review will highlight several molecular mechanisms of the progression of MDS to sAML and new therapeutic strategies of this disease.