Genomic loss of HLA alleles may affect the clinical outcome in low-risk myelodysplastic syndrome patients Genomic loss of HLA alleles may affect the clinical outcome in low-risk myelodysplastic syndrome patients

Optical genome mapping (OGM) is a novel, high-resolution technology for genome-wide detection of structural variants, offering clear advantages over conventional cytogenetics in hematologic malignancies. We applied OGM to a large cohort of patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDSs), and B-cell acute lymphoblastic leukemia (B-ALL) to evaluate its clinical utility. In AML and MDS, it revealed high-risk alterations such as deletions in 5q31–5q32 and 7q22, and cryptic fusions like NUP98::NSD1 that were missed by karyotyping or FISH. It also identified chromoanagenesis, a catastrophic chromosomal event linked to poor prognosis and often undetectable by standard methods. In B-ALL, OGM uncovered clinically relevant deletions in CDKN2A/B, PAX5, and IKZF1, as well as high-risk ploidy changes like hypodiploidy and hyperdiploidy, all important for risk assessment and frequently underdetected. OGM not only refines diagnosis and improves risk stratification but can also uncover cryptic and complex genomic abnormalities. Our findings support its integration into routine diagnostics to enhance classification, guide treatment decisions, and improve patient outcomes.

Background/Objectives: Chronic endometritis (CE) has been linked to implantation failure, recurrent pregnancy loss, and endometrial dysbiosis with low Lactobacillus abundance. We assessed the endometrial microbiota in infertile women with CE and the added value of combining intensified culturomics with 16S rDNA NGS. Methods: Cross-sectional study with descriptive results of 15 endometrial biopsies analyzed in parallel by intensified culture and 16S rDNA (V3–V6) sequencing (RA threshold ≥ 5%). Results: Culture yielded growth in 13/15 samples (86.7%), whereas NGS reported findings in 15/15 (100%). NGS provided additional taxa beyond culture in 14/15 (93.3%), while culture identified taxa missed by NGS in 10/15 (66.7%). In both culture-negative cases, NGS detected ≥1 taxon. Lactobacillus spp. appeared exclusively by NGS in 26.7% of samples; Fannyhessea vaginae showed the highest mean RA by NGS and did not grow in culture, underscoring complementarity. Conclusions: 16S NGS complements intensified culturomics for characterizing the endometrial microbiota in CE, enhancing detection—especially when culture is negative—and supports a combined, clinically contextualized interpretation. Larger, controlled cohorts are warranted to validate diagnostic and prognostic utility.

Natural killer (NK) cells play a key role in the innate immune response against viral infections. Their activity is regulated by a balance of activating and inhibitory signals, which are modulated by interactions with HLA class I molecules, including HLA-E. The HLA-B 21M/T dimorphism influences the availability of HLA-B leader peptides that stabilize HLA-E expression and modulate NK cell function via the NKG2A/CD94 receptor. To investigate the association between the HLA-B –21M/T dimorphism and the clinical severity of COVID-19, we analyzed a cohort of hospitalized patients with primary SARS-CoV-2 infection, who were genotyped for the HLA-B –21M/T dimorphism. Clinical data, lymphocyte counts, the neutrophil-to-lymphocyte ratio (NLR), and inflammatory markers were compared across genotypes. Contrary to previous studies suggesting a protective effect of the M/M genotype, we found no significant association between the HLA-B –21M/T dimorphism and COVID-19 severity, lymphocyte parameters, or inflammatory biomarkers. Our findings do not support a role for the HLA-B –21M/T dimorphism in modulating COVID-19 outcomes. These results underscore the complexity of NK cell regulation and highlight the need for integrative studies combining genetic, immunological, and functional data to better understand host factors influencing disease progression.