Dr. List’s work is focused on identifying pathogenetic mechanisms driving the biologic in myelodysplastic syndromes (MDS) to develop more effective and mechanistically based therapeutic strategies. In previous work, Dr. List had delineated the importance of angiogenesis in the pathobiology of MDS and selected a promising antiangiogenic agent (lenalidomide) from preclinical studies for clinical development. The work lead to FDA approval of this drug for the treatment of transfusion-dependent patients with MDS with the chromosome 5q deletion. The work focused on identifying specific drug targets with the MDS clone to further understand the biology of the disease and avenues for treatment. Dr. List and colleagues reported that the commonly deleted region involving the chromosome 5q interstitial deletion results in haploinsufficiency for two dual-specificity phosphatases, CDC25C and PP2A, which co-regulate the G2/M checkpoint. The work showed that lenalidomide inhibits the phosphatases encoded by the remaining allele to cause a selective G2 arrest and apoptosis, with consequent clonal suppression. Their most recent studies have shown that lenalidomide promotes p53 escape in deletion 5q MDS by suppressing autoubiquitination of MDM2 through PP2A inhibition, to later arrest cells in G2/M. They also showed that resistance to lenalidomide in patients with deletion 5q MDS arises from transcriptional upregulation of CDC25C and PP2A gene expression, with restoration of P53 activation within erythroid progenitors. These findings have led to a new therapeutic approach introducing an agent, ON-01910, which transcriptionally suppresses CDC25C, in early clinical development.