ZMYND11::MBTD1-rearranged acute myeloid leukemia in Chinese adolescents and adults: clinicopathologic features and clinical outcomes

The ZMYND11::MBTD1 fusion, resulting from t(10;17)(p15;q21), is a rare recurrent genetic alteration in acute myeloid leukemia (AML). Its clinical and prognostic features in adolescent and adult patients remain poorly characterized. This study aimed to delineate the clinicopathological, immunophenotypic, and molecular features, as well as treatment responses and survival outcomes, of patients harboring this fusion. We retrospectively analyzed five newly diagnosed AML patients aged ≥ 16 years with ZMYND11::MBTD1 fusion treated at our institution between 2020 and 2024. The five molecularly confirmed institutional cases were analyzed together with nine previously reported adult cases with t(10;17)(p15;q21)/ ZMYND11::MBTD1 -associated AML, yielding an integrated cohort of 14 patients. All institutional cases were identified via targeted RNA sequencing with PCR confirmation. Immunophenotyping, cytogenetics, treatment response, and overall survival (OS) were evaluated. All five institutional cases exhibited a consistent RAM-like immunophenotype characterized by bright aberrant CD7 and CD56 expression, positivity for CD33 and CD117, dim CD45, and absent or reduced HLA-DR and CD38. Conventional karyotyping detected t(10;17) in only one of five cases. In the institutional cohort, the complete remission (CR) rate after one induction cycle was 40%, with a best CR rate of 80% after sequential therapy. In the integrated cohort (median age 51 years, 57% female), 85.7% of patients were classified as ELN 2022 intermediate-risk. Among 13 patients evaluable for OS, median OS was 34.0 months. Patients who underwent allogeneic hematopoietic cell transplantation (allo-HCT) showed longer median OS (37.0 vs. 23.0 months) and 3-year OS (80.0% vs. 33.3%), but this comparison was limited by the small sample size and substantial treatment-selection heterogeneity. ZMYND11::MBTD1 - rearranged AML in adolescents and adults are characterized by a distinctive CD7/CD56-bright RAM-like immunophenotype and may be missed by conventional cytogenetic analysis. Recognition of this immunophenotypic pattern should prompt consideration of RNA-based fusion testing in diagnostically challenging cases. The observed clinical outcomes and the apparent association with allo-HCT are preliminary and hypothesis-generating and should not be interpreted as evidence of an independent adverse prognostic effect or a definitive transplant benefit. Larger multicenter cohorts are needed to define the prognostic significance and therapeutic implications of this rare fusion.