ABSTRACT
Staphylococcus lugdunensis (SL) is a well-known skin commensal. It is coagulase-negative bacteria that has often been labeled as a contaminant. While coagulase-negative bacteria are not as virulent as Staphylococcus aureus, there has been an increasing trend for this organism to be associated with complications commonly known to occur with its more aggressive counterpart. We report a case of Staphylococcus lugdunensis causing infective endocarditis and pseudoaneurysm of the aorta.
ABSTRACT
Proliferative chronic myelomonocytic leukemia (pCMML), an aggressive CMML subtype, is associated with dismal outcomes. RAS pathway mutations, mainly NRASG12D, define the pCMML phenotype as demonstrated by our exome sequencing, progenitor colony assays and a Vav-Cre-NrasG12D mouse model. Further, these mutations promote CMML transformation to acute myeloid leukemia. Using a multiomics platform and biochemical and molecular studies we show that in pCMML RAS pathway mutations are associated with a unique gene expression profile enriched in mitotic kinases such as polo-like kinase 1 (PLK1). PLK1 transcript levels are shown to be regulated by an unmutated lysine methyl-transferase (KMT2A) resulting in increased promoter monomethylation of lysine 4 of histone 3. Pharmacologic inhibition of PLK1 in RAS mutant patient-derived xenografts, demonstrates the utility of personalized biomarker-driven therapeutics in pCMML.
