Evaluation of p53 Expression in Megakaryocytes Enhances Detection of TP53 Mutations and Residual Disease in Myeloid Neoplasms

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Background and objective: Patients with TP53-mutated myeloid neoplasms have poor clinical outcomes, and studies evaluating p53 expression by immunohistochemistry (IHC) in treated disease are limited. This is the first study to assess p53 expression in megakaryocytes (MKs) compared with total bone marrow cells (TBMCs) and to examine its association with TP53 mutation status in both newly diagnosed/recurrent myeloid neoplasms and treated cases with residual disease. Methods: We evaluated 214 patients, including 130 with acute myeloid leukemia (AML), 61 with myelodysplastic neoplasm (MDS), and 23 negative controls. p53 expression by IHC was assessed in MKs and TBMCs and correlated with TP53 mutational status. Results: p53 expression in both MKs and TBMCs was significantly higher in TP53-mutated myeloid neoplasms than in TP53 wild-type cases and negative controls at diagnosis/recurrence. Evaluation of MKs improved IHC specificity from 0.91 to 0.98. In treated TP53-mutated cases, p53 expression in MKs and TBMCs correlated well with genetic and flow cytometry findings, with MK assessment also slightly improving sensitivity. Conclusion: p53 IHC is a rapid, cost-effective, and reliable tool for detecting TP53 aberrations and residual disease in myeloid neoplasms, particularly in settings with limited access to molecular testing. Concurrent evaluation of p53 expression in MKs and TBMCs improves both diagnostic specificity and sensitivity.