A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.

Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.

Racial disparities in timing and outcomes for patients undergoing staged single ventricle palliation: a single institution report.

Background: Racial disparities in healthcare have been well documented in the United States. We hypothesise that there will be a racial variance in different clinical variables in single-ventricle patients through stages of palliation.

Materials And Methods: Retrospective single-centre study stratified all single-ventricle patients who reached stage 2 palliation by race: Black and White.

Revealing the Demographic History of the European Nightjar ().

A species' demographic history gives important context to contemporary population genetics and a possible insight into past responses to climate change; with an individual's genome providing a window into the evolutionary history of contemporary populations. Pairwise sequentially Markovian coalescent (PSMC) analysis uses information from a single genome to derive fluctuations in effective population size change over the last ~5 million years. Here, we apply PSMC analysis to two European nightjar () genomes, sampled in Northwest and Southern Europe, with the aim of revealing the demographic history of nightjar in Europe.

Clonal Evolution in 207 Cases of Refractory or Relapsed Acute Myeloid Leukemia.

Clonal evolution (CE) is a driving force behind the development and progression of acute myeloid leukemia (AML). Advances in molecular and cytogenetic assays have improved the depth and breadth of detection of CE in AML, which is defined here as a detected change in cytogenetic or molecular profile at relapsed or refractory (RR) disease. In this study, we demonstrate the clinical impact of CE in a cohort of patients with RR AML treated between 2013 and 2023.