Molecular pathogenesis of myelodysplastic syndromes with deletion 5q.

Abstract

The molecular pathogenesis of deletion 5q (del(5q)) myelodysplastic syndrome (MDS) has recently been realized as a result of major advances in our understanding of the mechanisms responsible for clinical phenotype. Identification of commonly deleted genes such as RPS14, miRNA-145, HSPA9, CD78, and CSNK1a1 have elucidated the precise biological changes responsible for the anemia, leukopenia, and thrombocytosis that characterizes del(5q) MDS and highlighted the importance of allelic haploinsufficiency in the hematological phenotype. Recent elegant investigations have also identified a critical role of innate immune signaling in del(5q) pathogenesis. TP53 and Wnt/β-catenin pathways have also been found to be involved in clonal expansion and progression of the disease as well as resistance and poor outcomes to available therapy. Understanding the molecular pathogenesis of the disease has provided a critical foundation in identifying the biological targets of lenalidomide in del(5q) MDS, which has led to the development of novel therapeutic agents in hematologic malignancies as well as potential alternative targets to exploit in patients who have failed lenalidomide treatment.