Status: Pending
Significant advancements in understanding leukemia development have primarily stemmed from characterizing somatic alterations over the last few decades. However, the recognition of the role of germline mutations in driving the development of acute leukemia has been increasingly acknowledged. Numerous germline mutations implicated in the development of both familial and sporadic hematological malignancies have been documented in the literature. These mutations involve genes encoding transcription factors such as RUNX1, CEBPA, or GATA2; MECOM, genes involved in promoting MAPK signaling and megakaryocyte development like ANKRD26, or interferon-inducible genes such as SAMD9 or SAMD9L. Many of these genes with germline mutations predisposing to myeloid or lymphoid leukemia are the same as those frequently disrupted by somatic mutations in these diseases (e.g., TP53, RUNX1, IKZF1, and ETV6). In this project, our objective is to conduct a preliminary characterization of leukemia cases potentially linked to existing germline mutations inferred from patient or familial contexts. Inclusion criteria for this study have been clearly defined following close collaboration with leukemia-treating physicians. Consenting parent-patient trios will undergo Whole-Exome-Sequencing and bioinformatic analysis of the generated datasets. We anticipate completing Five Parent-Patient trios in this project. The bioinformatic pipeline encompasses a comprehensive list of genes involved in cancer, including known cancer/leukemia-predisposing genes as reported in peer-reviewed publications. Our research aims to seek preliminary results of investigation of germline predisposition variation in leukemia. Thanks to IP support for Ethical and authorizations processes and to France genomique for fundings.
Submitted: 2025-01-10 07:22 · Last updated: 2026-01-19 13:42