ABSTRACT Background Survivors of childhood acute leukemia are at risk of long‐term treatment‐related complications, but the role of genetic susceptibility remains unclear. We describe here the GenLEA project, which was established to investigate genetic determinants of long‐term complications. Methods GenLEA builds on the French LEA cohort, which prospectively follows acute leukemia survivors since 2004 through standardized dedicated consultations every 2 to 4 years. Patients were selected from the nested CryoLEA biobank. Cases were defined as survivors with at least one of four major complications (anthracycline‐related cardiomyopathy, secondary malignant neoplasms, metabolic syndrome, or osteonecrosis) while controls were survivors without these complications, selected with the objective of a 1:3 case‐to‐control ratio. Genetic data were generated using genome‐wide genotyping and whole‐exome sequencing. Results After quality control, 743 patients were included for analyses (241 cases and 502 controls). Fifty‐one percent were male with a median age at diagnosis of 7.3 years (IQR 3.9–13.0), and median follow‐up reached 14 years (IQR 7.9–19.8). Among the cases, 44 had cardiomyopathy, 50 osteonecrosis, 37 secondary malignant neoplasms, and 163 metabolic syndrome. Planned analyses include genome‐wide association studies (GWAS) and downstream analyses such as transcriptome‐wide association studies (TWAS) and Mendelian randomization on genotyping data, as well as gene‐based tests on exome sequencing data. Perspectives By integrating these approaches with high‐quality clinical information, GenLEA offers a unique opportunity to identify molecular determinants of late complications after childhood acute leukemia. This collaborative resource will support replication efforts, meta‐analyses, and ultimately the development of personalized long‐term follow‐up strategies.
Veneziano‐Broccia et al. (Sun,) studied this question.