Background: The 2023/2024 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for myeloid malignancies, alongside the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms, and the 2022 International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (ICC), provide comprehensive frameworks for understanding the genetic landscape of these diseases. This study aims to compare the genetic references in these guidelines to highlight the breadth of genetic markers implicated in myeloid malignancies.

Methods: We systematically reviewed the NCCN guidelines, the WHO, and the ICC system for references to genes relevant to myeloid neoplasms. The myeloid neoplasms assessed included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), MDS/MPN overlap syndromes, chronic neutrophilic leukemia (CNL), and chronic eosinophilic leukemia (CEL).

Results: A total of 185 unique genes were identified as relevant to myeloid malignancies within the guidelines, 87 of which were fusions. 89 genes were mentioned in the NCCN guidelines, 74 in the WHO classification, and 143 in the ICC. Some genes were uniquely associated with specific disease states, while others were relevant across various myeloid malignancies. An overlap of 76 genes, including 32 fusions was noted across all guidelines.

Conclusion: The findings underscore the critical role of comprehensive genetic testing in the diagnosis and management of myeloid malignancies. The overlap and unique genetic markers identified in the NCCN, WHO, and ICC guidelines emphasize the need for large panel testing across myeloid malignancies to ensure precise genetic characterization of the relevant genes, enabling accurate diagnosis, risk stratification, prognostication, and the tailoring of therapeutic strategies to the patient, including the use of drugs targeted for only certain mutations. The high gene count captured within the treatment guidelines emphasizes the necessity for comprehensive genetic testing to enhance clinical outcomes and advance personalized medicine in the management of myeloid neoplasms.

Disclosures

Puentes:NeoGenomics: Current Employment, Current equity holder in publicly-traded company. Feld:Syros Pharmaceuticals: Research Funding; Oryzon Genomics: Research Funding; Taiho Pharmaceutical: Research Funding. Smith:NeoGenomics: Current Employment. Lyle:Neogenomics: Current Employment, Current equity holder in publicly-traded company.

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2024
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