[Hereditary diseases with propensity to myeloid malignancy].

Area of Science:

• Hematology
• Oncology
• Genetics

Context:

• Down syndrome (DS), neurofibromatosis type 1 (NF1), and congenital bone marrow failure syndromes (CBMFS) are associated with a higher incidence of hematological malignancies.
• Germline mutations predisposing to these conditions are known, but secondary mutations driving leukemogenesis remain largely uncharacterized.

Purpose:

• To review recent findings on genetic alterations contributing to the development of myelodysplastic syndrome and acute myelogenous leukemia (MDS/AML) in individuals with DS, NF1, and CBMFS.
• To highlight the role of secondary mutations and chromosomal abnormalities in disease progression.

Summary:

• Hematological malignancies, including MDS/AML, frequently occur in individuals with specific genetic syndromes like DS, NF1, and CBMFS.
• While germline mutations are identified, secondary mutations and chromosomal abnormalities (e.g., monosomy 7, trisomy 21) are critical for the progression to MDS/AML.
• Recent research is beginning to elucidate the specific genes involved, particularly for monosomy 7.

Impact:

• This review synthesizes current knowledge on the molecular basis of leukemogenesis in high-risk genetic syndromes.
• Understanding these secondary mutations can inform diagnostic strategies and potentially lead to targeted therapies for MDS/AML in affected populations.
• Provides a foundation for future research into the specific genetic drivers of myeloid malignancies in these syndromes.