Work

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

Year: 2026

Type: article

Abstract: Background 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 adult patients remain poorly characterized, particularly in Chinese populations. This study aimed to delineate the clinicopathological, immunophenotypic, and molecular features, as well as treatment responses and survival outcomes, of adult AML harboring this fusion. Methods We retrospectively analyzed five newly diagnosed adult AML patients with ZMYND11::MBTD1 fusion treated at our institution between 2020 and 2024. These cases were integrated with nine previously reported adult cases for a comprehensive cohort analysis (N = 14). All institutional cases were identified via targeted RNA sequencing with PCR confirmation. Immunophenotyping, cytogenetics, treatment response, and overall survival (OS) were evaluated. Results 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. The median OS was 34.0 months, with estimated 1-, 2-, and 3-year OS rates of 83.3%, 60.8%, and 48.6%, respectively. Patients who underwent allogeneic hematopoietic cell transplantation (allo-HCT) showed numerically longer median OS (37.0 vs. 23.0 months) and 3-year OS (80.0% vs. 33.3%), though not statistically significant ( P = 0.472). Conclusion Adult AML with ZMYND11::MBTD1 fusion displays a distinctive RAM-like immunophenotype and an unfavorable clinical course that may not be fully captured by current ELN risk stratification. Recognition of this entity, particularly in cases with bright CD7/CD56 expression, is clinically important. Early consideration of allo-HCT may be warranted in eligible patients, and larger prospective studies are needed to validate these findings and refine risk assessment.

Source: BMC Cancer

DOI: 10.1186/s12885-026-16938-8