Editor's Note: Some of the articles described below are not yet available at the PNAS site but are scheduled to be posted this week.
Investigators at the University of Tübingen, the University of Pennsylvania, and elsewhere characterize structural variants involved in an X chromosome-linked, recessively inherited congenital retinal condition known as blue cone monochromacy, which is tied to an X chromosome gene cluster containing OPN1LW/OPN1MW. Using PCR-based screening, the team searched for structural variants in 213 blue cone monochromacy-affected families, uncovering 42 distinct structural variants in 73 families and teasing out breakpoint sequences. "Our study expands the known spectrum of structural mutations causing [blue cone monochromacy] by a factor of four and provides a comprehensive landscape of their extent and fine structure as well as a deep insight into the underlying molecular mechanisms," they write.
A team from Italy, Australia, and the US look at increasingly common HIV-1 mutants that contain amino acid insertions affecting the matrix protein p17. By examining nearly 4,000 HIV-1 sequences spanning several decades, from the mid-1980s to 2017, the investigators saw an uptick in p17 variant-expressing proteins in recent years. They also highlighted a clonogenic form of HIV variant-expressing B cells that have turned up in the last decade, potentially influencing lymphatic vessel formation and blood cancer risk. "[W]e conclude that [amino acid] insertions can be fixed in HIV-1 and that mutant viruses displaying B cell clonogenic [variant p17s] are actively spreading," the authors write, noting that "[e]arly identification of clonogenic vp17s would make it possible to implement therapeutic or preventive strategies to avoid their long-term cancer-promoting activity."
Researchers from the University of Missouri-Columbia and Mayo Clinic College of Medicine in Rochester suggest that NOTCH-mutated T-cell acute lymphoblastic leukemia (T-ALL) development involves major histocompatibility complex and alpha-beta T-cell antigen receptor signaling in a subset of immature thymocyte cells in the process of becoming T immune cells. With cell line, mouse model, and other experiments, the team found that "unique developmental states provide unique context and signaling rules" influencing not only precursor T cell reactivity, but also T-ALL leukemogenesis. "It is likely that a deeper understanding of both overlapping and disparate mechanisms driving T-ALL between different models and thymocyte stages will create more knowledge surrounding the heterogeneity of T-ALL clinical phenotypes," they write.