Conventional PCR Versus Next Generation Sequencing for Diagnosis of FLT3, IDH and NPM1 Mutations in Acute Myeloid Leukemia: Results of the PETHEMA PCR-LMA Study.

Background/objectives: This PETHEMA PCR-LMA study aimed to evaluate whether mutations detected by NGS (VAF cut-off of ≥5%) correlate with NPM1, FLT3-ITD, FLT3-TKD, IDH1, and IDH2 mutations detected using conventional PCR (analytical sensitivity 3%) in a nationwide network of seven reference laboratories.

Methods: Between 2019 and 2021, 1685 adult AML patients with at least one centralized sample (NGS or PCR) at primary diagnosis or relapse/refractory episode were included.

Results: During this period, 1288 paired NGS/PCR samples (1094 at diagnosis, 103 at relapse and 88 at refractoriness) were analyzed.

Mitochondrial-Mediated Platelet Activation in Polymyalgia Rheumatica.

Objective: Platelet activation is thought to participate in polymyalgia rheumatica (PMR) pathogenesis. Upon platelet activation, mitochondria are expelled into the extracellular space. However, whether extracellular mitochondria are present in patients with PMR and whether they can induce platelet activation is not known.

Competition for shared resources increases dependence on initial population size during coalescence of gut microbial communities.

The long-term success of introduced populations depends on both their initial size and ability to compete against existing residents, but it remains unclear how these factors collectively shape colonization dynamics. Here, we investigate how initial population (propagule) size shapes the outcome of community coalescence by systematically mixing eight pairs of in vitro microbial communities at ratios that vary over six orders of magnitude, and we compare our results to neutral ecological theory. Although the composition of the resulting cocultures deviated substantially from neutral expectations, each coculture contained species whose relative abundance depended on propagule size even after ~40 generations of growth.

The MEF2D::NCOA2 Fusion Defines a Distinct Emerging Vulvovaginal Myxoid Epithelioid Tumor with Smooth Muscle Differentiation.

MEF2D::NCOA2 fusion was recently reported in two vulvovaginal myxoid epithelioid smooth muscle tumors. We aimed to performed an integrated approach combining clinical, morphological, immunohistochemical, and molecular profiling analyses, including targeted-RNA-sequencing, targeted-gene expression analysis profiling with clustering, DNA mutational analysis, and array comparative genomic hybridization (aCGH) in a series of three MEF2D::NCOA2 fusion-associated vulvovaginal tumors, to better described this entity. The median age at diagnosis was 45 years.

ZEB1 transcription factor induces tumor cell PD-L1 expression in melanoma.

Tumor cells can evade antitumor immune response by expressing the PD-L1 ligand, leading to the inhibition of PD-1-expressing T lymphocytes. The mechanisms that regulate PD-L1 expression in cancer cells are imperfectly characterized. The transcription factor ZEB1, a major regulator of phenotype switching in melanoma cells, was shown to promote immune escape in melanoma by repressing T cell infiltration.