Polycystic kidney disease (PKD) is a major cause of end-stage renal disease. The disease mechanisms are not well understood and the pathogenesis toward renal failure remains elusive. In this study, we present the first RNASeq analysis of a -mutant mouse model in a combined meta-analysis with other published PKD expression profiles. We introduce the PKD Signature, a set of 1,515 genes that are commonly dysregulated in PKD studies. We show that the signature genes include many known and novel PKD-related genes and functions. Moreover, genes with a role in injury repair, as evidenced by expression data and/or automated literature analysis, were significantly enriched in the PKD Signature, with 35% of the PKD Signature genes being directly implicated in injury repair. NF-κB signaling, epithelial-mesenchymal transition, inflammatory response, hypoxia, and metabolism were among the most prominent injury or repair-related biological processes with a role in the PKD etiology. Novel PKD genes with a role in PKD and in injury were confirmed in another-mutant mouse model as well as in animals treated with a nephrotoxic agent. We propose that compounds that can modulate the injury-repair response could be valuable drug candidates for PKD treatment.

No abstract

Patients with therapy-related acute myeloid leukemia (t-AML) and myelodysplastic syndromes (t-MDS) have poor survival and high non-relapse mortality (NRM) after allogeneic stem cell transplantation. This retrospective study assessed the transplant outcomes of 29 consecutive patients with t-AML (83%) or t-MDS (17%) treated with allogeneic transplantation. The median age of patients was 51 years. Donors were mostly matched unrelated (52%), and 59% of patients received myeloablative conditioning. Two-year overall survival, event-free survival and relapse incidence were 37%, 34% and 33%; NRM was 17% at 100 days, and 32% at 2 years. Event-free survival was reduced in patients with high-risk cytogenetics (p = 0.02), Karnofsky performance status ≤ 80% (p = 0.001) and disease after induction ± consolidation (p = 0.006). NRM was higher in patients receiving > 2 therapy lines for previous cancer (p = 0.01) and in those allografted > 6 months from diagnosis (p = 0.03). In conclusion, allogeneic transplantation should be proposed timely to these patients after an accurate analysis of patient history.

No abstract