Biomedical subjects

Elsa Bernard

Publications and source records attributed to Elsa Bernard.

3 recordsLinked to original sources

PubMed2026

Risk Prognostication After Hypomethylating Agents Combined With Venetoclax in AML: The PRISM Risk Model.

PURPOSE: As risk stratification for patients with AML treated with lower-intensity venetoclax-based therapy remains suboptimal, we developed and validated a prognostic model integrating clinical, cytogenetic, and molecular features. METHODS: We assembled a multinational data set comprising 2,092 adults with newly diagnosed AML treated with hypomethylating agents plus venetoclax (HMA + VEN). One thousand nine hundred eighteen patients with complete data were randomly divided into training (70%) and internal validation (30%) cohorts. Two independent external validation cohorts were assembled (n = 500 and n = 222). Modeling overall survival (OS), Elastic Net regression was applied in 1,000 bootstrap samples from the training cohort to select variables for a Ridge regression, which generated a continuous Prognostic Risk Integration for Survival Modeling (PRISM) score and risk categories based on tertiles (PRISM-3: low, moderate, high). These PRISM indices were then computed for the validation cohorts and compared with the 4-gene classifier (based on mutations in FLT3-ITD, N/KRAS, and TP53). RESULTS: PRISM integrated 17 clinical and genomic variables and demonstrated a linear association with OS. PRISM-3 stratified survival consistently across all cohorts (median OS: 25.1-28.8 months for low risk, 12.5-14.7 months for moderate risk, and 5.8-6.7 months for high risk; P < .001). Compared with the 4-gene classifier, PRISM-3 reassigned approximately 40% of patients (and >50% of those with favorable risk) and demonstrated significantly better discrimination in validation cohorts (C-index 0.63-0.65 v 0.59-0.61; P < .05). CONCLUSION: PRISM is a validated prognostic model for patients with AML receiving HMA + VEN that improves survival risk stratification beyond current standard tools and supports individualized, risk-adapted clinical decision making. The model, the PRISM-AML Risk Calculator, is publicly available.

Humans↗

PubMed2026

fRagmentomics: an R package for integrating cell-free DNA fragment features with mutational status to support liquid biopsy interpretation.

SUMMARY: Liquid biopsy offers a non-invasive approach to study tumor-derived genetic material circulating in plasma. Beyond genetic alterations, the fragmentomic features of cell-free DNA-such as fragment size, genomic position, and end-motifs-provide valuable insights into the biological and clinical context of DNA release. fRagmentomics is a user-friendly R package designed to characterize cfDNA fragments overlapping one or multiple small mutations of any type, starting from an aligned sequencing file (BAM). It supports multiple mutation input formats, accommodates one-based and zero-based genomic conventions, resolves mutation representation ambiguities, and accepts any reference file in FASTA format. For each fragment overlapping a mutation of interest, fRagmentomics outputs fragment-level features including its fragment size, end-motifs, and mutational status, along with additional fragment-level or read-level information. The package implements an indel-aware and optionally soft-clip-preserving fragment size computation that improves accuracy over conventional size estimates based solely on aligned positions. AVAILABILITY AND IMPLEMENTATION: fRagmentomics is licensed under GNU General Public License v3.0 and available at https://github.com/ElsaB-Lab/fRagmentomics, https://anaconda.org/elsab-lab/r-fragmentomics and https://bioconductor.org/packages/fRagmentomics, with documentation and a tutorial. CONTACT: yoann.pradat@gustaveroussy.fr, elsa.bernard@gustaveroussy.fr. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Software↗

PubMed2025

Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia.

Isocitrate dehydrogenase 1/2 (IDH) mutations are early initiating events in acute myeloid leukemia (AML). The complex clonal architecture and cellular heterogeneity in IDH-mutant AML underlies the heterogeneous clinical presentation and outcomes. Integrating single-cell genotyping and transcriptomics, we demonstrate a stem-like and inflammatory phenotype of IDH-mutant AML and identify clone-specific programs associated with NPM1, NRAS, and SRSF2 co-mutations. Furthermore, these clones had distinct responses to treatment with combination IDH inhibitors and chemotherapy, including elimination, reconstitution of myeloid differentiation, or retention within progenitor populations. At relapse after IDH inhibitor monotherapy, we identify upregulated stemness, inflammation, mitochondrial metabolism, and anti-apoptotic factors, as well as downregulated major histocompatibility complex (MHC) class II antigen presentation. At the pre-leukemic stage, we observe upregulation of IDH2-associated pathways, including inflammation. We deliver a detailed phenotyping of IDH-mutant AML and a framework for dissecting contributions of recurrently mutated genes in AML at diagnosis and following therapy, with implications for precision medicine.

Leukemia, Myeloid, Acute↗