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Annual Review of Pathology: Mechanisms of Disease

Volume 20, 2025

Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications

Abstract

Myeloid neoplasms with and without preexisting platelet disorders frequently develop in association with an underlying germline predisposition. Germline alterations affecting , , , , and are associated with nonsyndromic predisposition to the development of myeloid neoplasms including acute myeloid leukemia and myelodysplastic syndrome. However, germline predisposition to myeloid neoplasms is also associated with a wide range of other syndromes, including / associated predisposition, deficiency, RASopathies, ribosomopathies, telomere biology disorders, Fanconi anemia, severe congenital neutropenia, Down syndrome, and others. In the fifth edition of the World Health Organization (WHO) series on the classification of tumors of hematopoietic and lymphoid tissues, myeloid neoplasms associated with germline predisposition have been recognized as a separate entity. Here, we review several disorders from this WHO entity as well as other related conditions with an emphasis on the molecular pathogenesis of disease and accompanying somatic alterations. Finally, we provide an overview of establishing the molecular diagnosis of these germline genetic conditions and general recommendations for screening and management of the associated hematologic conditions.

Keyword(s): acute myeloid leukemia, bone marrow failure, germline genetics, myelodysplastic syndrome, myeloid neoplasm, thrombocytopenia
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/content/journals/10.1146/annurev-pathmechdis-111523-023420
2025-01-24
2025-04-30
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/content/journals/10.1146/annurev-pathmechdis-111523-023420
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Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications
Annual Review of Pathology: Mechanisms of Disease 20, 87 (2025); https://doi.org/10.1146/annurev-pathmechdis-111523-023420
/content/journals/10.1146/annurev-pathmechdis-111523-023420
/content/journals/10.1146/annurev-pathmechdis-111523-023420
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  • Article Type: Review Article

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