Cytogenetic subtypes of MDS – Molecular background, prognostic relevance and therapeutic consequences

SummaryMyelodysplastic syndromes show a profound heterogeneity regarding not only morphological features and clinical course but also cytogenetic findings. The great prognostic relevance of cytogenetics is generally appreciated, however, it is only known for the most frequent karyotype abnormalities, not for combinations of anomalies and not for more rare changes. To overcome these limitations multicentric cooperations are needed. Nevertheless, recent clinical and basic research allows for a delineation of myelodysplastic syndromes (MDS) subtypes defined by the most frequent chromosomal changes. Recently, the German–Austrian MDS study-group presented a database of cytogenetic findings in 2072 patients with MDS which serves as a basis for the characterization of the cytogenetic subgroups discussed in this article. In this analysis, 52.1% of patients displayed clonal chromosome abnormalities. The most frequent changes were 5q- (29% of abnormal cases), complex changes (27%), -7/7q- (24%), +8 (16%), 20q- (7%), -Y (5%). The advent of new therapeutic options for MDS targeted on distinct entities characterized by a specific chromosome abnormality, as shown paradigmatically for lenalidomide in patients with 5q- syndrome, underlines the important role of cytogenetics for the clinical management of MDS.The following cytogenetic subtypes will be presented in detail: subgroups (favourable, intermediate, unfavourable) defined by the International Prognostic Scoring System (IPSS), 5q-deletions, monosomy 7, and complex abnormalities. The discussion of these cyogenetic entities is focused on prognostic relevance, molecular background and recently established as well as potential future therapeutic strategies which may have promising potential and are feasible not only in low-risk MDS but also in high-risk myelodysplasia of elderly patients.