KEY TAKEAWAYS
- The study aimed to underscore the importance of accurate identification of familial myeloid neoplasms for better clinical management.
- The study highlighted that underestimating genetic predisposition necessitates improved family history reconstruction and genetic testing.
Myeloid neoplasms, such as acute myeloid leukemia (AML), have historically been less studied in terms of germline predisposition. Identifying these cases is challenging due to their clinical and morphological similarities to sporadic cases and comparable age at diagnosis.
Chiara Ronchini and the team aimed to highlight the importance of accurately identifying familial myeloid neoplasms, as misidentification can significantly impact clinical management for both carriers and their relatives.
Researchers conducted a family segregation study to find new cancer-predisposing genes in myeloid neoplasms using the Myelo-Panel, a 256-gene custom panel. They analyzed germline and somatic variants in four families, each with 2 siblings diagnosed with hematological neoplasms.
The results showed seven cases of AML and one case of Philadelphia-positive chronic myeloid leukemia. They found at least 1 novel potentially predisposing variant in each family, including genes outside the current European LeukemiaNet guidelines. Additionally, they suggest reclassifying 2 germline variants as pathogenic: likely pathogenic p.S21Tfs*139 in CEPBA and VUS p.K392Afs*66 in DDX41.
The study concluded that the predisposition to hematological neoplasms is often underestimated and challenging to diagnose. It emphasizes the need for revised clinical practices, including comprehensive family history reconstruction and detailed genetic testing, to improve management for carriers and their relatives.
The study was partially funded by the Italian Ministry of Health.
Source: https://pubmed.ncbi.nlm.nih.gov/39118233/
Ronchini C, Gigli F, Fontanini M, et al. (2024). “Identification of Novel Potential Predisposing Variants in Familial Acute Myeloid Leukemia.” Cancer Rep (Hoboken). 2024 Aug;7(8):e2141. doi: 10.1002/cnr2.2141. PMID: 39118233.
