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PNAS Papers on Transcriptome-Based T-ALL Subtypes, Estrogen Receptor Regulators, More

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.

An international team led by investigators at Shanghai Jiao Tong University shares findings from a transcriptomic analysis of T cell acute lymphoblastic leukemia (T-ALL) subtypes. The investigators tracked down 10 transcriptome-based subtypes with RNA sequencing on 707 pediatric and adult T-ALL, including a new GATA3-mutated subtype and subtypes with a wide range of other gene mutation, expression, and affected T cell stages. "Adult T-ALL tends to have characteristics of early T cell precursor ALL, mostly corresponding to the mixed phenotype acute leukemia, whereas pediatric T-ALL shows a wide spectrum of aberrant molecular features, from early T cell precursor to mature T cell compartments," they report. "Our findings have important implications for disease mechanism[s] of T-ALL that differs between pediatric and adult patients, facilitating further refined targeted therapy."

Researchers at Yamaguchi University and other centers in Japan propose prognostic roles for the FKBP52 and FKBP51 genes in estrogen receptor-positive forms of breast cancer. The team flagged the prognostic candidate genes through transcriptomic, interactome, and survival analyses of available ER-positive forms of breast cancer, subsequently turning to a series of breast cancer cell line and mouse xenograft model experiments to uncover distinct estrogen receptor-alpha stability effects for each gene. While FKBP52 appeared to stabilize ER-alpha stability, boosting the proliferation of ER-positive breast cancer cells, the authors found that FKBP51 gene product was expressed more robustly in normal tissue and seemed to dial down ER-alpha stability. "We found that two immunophilins, FKBP52 and FKBP51, have opposing effects on ER-alpha stability and propose that therapeutic targeting of FKBP52 could be useful for the prevention and treatment of ER-alpha-positive breast cancers," they write, "including endocrine therapy-resistant breast cancers."

A National Institute of Health team describes the detection of a non-invasive, imaging-based approach for tracking organ-level Ebola virus (EBOV) infection effects or progression using a translocator protein (TSPO) immune cell marker. The researchers relied on a positron emission tomography (PET) imaging to quantify TSPO levels in different organ systems over time in an EBOV-infected Rhesus macaque model, comparing the results to post-mortem tissue testing and to multiplex fluorescence immunohistochemistry-based biomarker profiles in blood samples obtained prior to the imaging sessions. "This study provides real-time non-invasive assessment of EBOV pathogenesis and disease progression, as well as the associated host responses, at the organ level," the authors explain, adding that the approach "can be similarly used to study other inflammatory and infectious diseases and to test the efficacy of newly developed therapeutics and vaccines."

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