Skip to main content
Premium Trial:

Request an Annual Quote

PNAS Papers on Rearranged-AML Mutations, Hepatocellular Carcinoma Model, Brucella

Researchers from Ohio State University Comprehensive Cancer Center, the University of Alberta, and elsewhere explore the broader mutation patterns found in acute myeloid leukemia (AML) tumors marked by recurrent balanced chromosome 11 rearrangements involving the KMT2A gene. Using targeted panel sequencing, targeted amplicon sequencing, and clinical outcome data, when available, the team assessed up to 172 AML cases with 11q23/KMT2A rearrangements, setting them against mutational patterns in nearly 1,100 11q23/KMT2A rearrangement-free AML cases. Along with RAS pathway mutations in nearly one-third of the tumors with the rearrangement, for example, the data pointed to better-than-usual outcomes in younger AML patients with chromosome 11 arrangements involving KMT2A and the MLLT3 gene. "Our study shows that patients with an 11q23/KMT2A rearrangement have distinct mutational patterns and outcomes depending on the fusion partner," the authors report.

A team from Tongji University and other centers in China take a look at DNA double-strand break repair patterns in tumor and normal samples from mouse models of the liver cancer hepatocellular carcinoma (HCC). The researchers relied on a knock-in reporter approach to track DNA double strand break repair, along with activity by the homologous recombination (HR) and non-homologous end-joining (NHEJ) double-strand break repair pathways in control mice and in mice with chemically induced forms of HCC. Their results point to a rise in both HR and NHEJ double-strand break repair in the tumor tissue, along with shifts in PARP1 expression and the expression of other genes influencing DNA repair. From these and other results, including experiments with inhibitors blocking each of the double-strand break repair pathways, the authors suggest that HCC may be susceptible to treatments targeting the up-regulated pathways. "Our work not only establishes versatile tools for in vivoanalysis of DNA repair," they write, "but also implies an effective combination therapy for HCC."

An international team led by investigators in Belgium, France, and the US describe metabolic features that converge in a handful of pathogenic Brucella bacterial species. With a combination of genome sequences, phylogenetic analyses, and stable isotope labeling-based amino acid profiling, the researchers compared central metabolic features across seven Brucella species, identifying two groups of species that do or do not rely on a pentose phosphate pathway (PPP) for hexose catabolism — a pathway previously proposed as a potential marker for pathogenic forms of the bacteria, known for infecting domestic livestock and humans. "This metabolic dichotomy arose after the acquisition of two newly identified [Entner-Doudoroff metabolic pathway]-inactivating mutations," they report, noting that "[t]his selected trait seems to be linked to bacterial pathogenicity in mice."