At the heart of unmet need: TP53 myeloid neoplasms

TP53 myeloid neoplasms are being increasingly encountered in clinical practice and have been recognised in 2022, as a unique entity in the setting of functional loss of the two copies of the gene. The classification of myeloid neoplasm based on presence of biallelic (multi-hit) TP53 should precede morphological classification. The identification of biallelic (multi-hit) inactivation continues to evolve and is a matter of great debate balancing definitive biallelic identification via assays, pathology classifications, and clinical applicability. There is clear interplay between myeloblast percentage, TP53 allelic state, and cytogenetics as most TP53 cases encountered (~90%) are associated with poor outcomes driven by those variables and can be approached similarly. Only a small subset of individuals with monoallelic (single-hit) TP53 mutation status and no concomitant increased myeloblasts or complex cytogenetics have better outcomes and perhaps can be managed as non-TP53 cases. In this paper, we review definition and classification of TP53 myeloid neoplasms, highlight outcomes, and discuss the current standard of care and clinical research efforts crucially needed for this subtype of disease.