Mesothelin Expression in Acute Leukemia: Correlations With Immunophenotype, Cytogenetics, and Mutational Status

Mesothelin is a surface glycoprotein overexpressed in several solid tumors and a known immunotherapy target. While present on blast cells in acute myeloid leukemia (AML), its role in acute lymphoblastic leukemia (ALL) remains unclear. This study evaluated mesothelin expression in 181 newly diagnosed acute leukemia cases using immunohistochemistry (IHC) on bone marrow biopsies and ELISA on plasma samples. Mesothelin was expressed in 31% of pediatric and 15% of adult AML cases (n=65), with no significant differences among AML subtypes. It was absent or rare in ALL (n=51) and undetectable in normal bone marrow. In AML, mesothelin was detected in 49% of CD38⁺, 60% of CD64⁺, 62.5% of KMT2A-rearranged, and 69% of core binding factor AML [83% with inv(16)/t(16;16), 57% with t(8;21)]. It was largely absent in cases with NPM1 (87.5%), GATA2, and DNMT3A mutations. Expression correlated significantly with age, CD38, CD64, and mutations in NPM1, GATA2, DNMT3A, and KDM6A. No significant association was found between mesothelin expression and 5-year overall or event-free survival, measurable residual disease, remission, or relapse. In ALL, 83.3% of T-ALL and 85% of B-ALL cases showed no expression. However, mesothelin correlated with CD11c, PHF6, and CBLC mutations in ALL. Soluble mesothelin was present in 17.6% of AML and 2.7% of ALL cases (all adults), but not in healthy individuals. In AML, it correlated with CD33 expression and inv(16)/t(16;16). In conclusion, mesothelin is rare in ALL but enriched in specific AML subtypes and not prognostic for survival.