Can molecular profiling of cytogenetic subgroups draw a roadmap for individualizing therapy in myelodysplastic syndromes?

Therapeutic options for the heterogeneous hematopoietic disorders grouped under the myelodysplastic syndromes (MDS) have been difficult to develop, even though the incidence of this disease is increasing because of the ageing population. Several drugs have now been shown to have therapeutic efficacy in subgroups of patients, but the main challenge is still the preselection of the patient for a given strategy. To state the problem simply, effective therapies may already exist for a substantial number of MDS patients, but we do not know how to match the right drug to the right patient. Cytogenetic abnormalities have provided some treatment guidance, however these are generally restricted to patients known to have a better prognosis. To develop reliable predictive assays in patients with complex or more advanced diseases, we will have to delve deeper than cytogenetics. This review summarizes what is known about the clinical and biological characteristics of various karyotypic subgroups of MDS, and proposes a roadmap for combining the bedside-to-bench approach with the use of DNA microarray analysis in developing expression profiles that can serve as a guide in the preselection of treatment options for individual MDS patients.