ARID1B 突变通过上调 VISTA 表达促进急性髓系白血病的免疫逃逸

Acute myeloid leukemia (AML) is defined by epigenetic heterogeneity, and recurrent mutations in chromatin remodelers are associated with a poor prognosis. Whether these mutations drive treatment resistance through remodeling of the tumor immune microenvironment remains unclear. ARID1B, a recurrently mutated SWI/SNF subunit in AML, has an uncertain association with adverse outcomes, and its immunomodulatory role remains undefined.

This study characterized the clinical, genomic, and immunological features of ARID1B-mutant AML and assessed their impact on treatment response and prognosis. ARID1B mutations displayed clinical heterogeneity. Patients harboring the p.

Gly332_Ala336del variant achieved significantly higher rates of complete remission and overall response to induction chemotherapy compared with those carrying other ARID1B mutations. Prognostic impact was context-dependent: ARID1B mutation conferred inferior survival specifically in acute promyelocytic leukemia and in patients aged ≥65 years.

Mechanistically, ARID1B mutations were associated with an immunosuppressive microenvironment, characterized by upregulated VISTA expression on leukemic blasts, reduced bone marrow CD8 + T-cell infiltration, and impaired effector function of both CD8 + T cells and NK cells.

These findings suggest that ARID1B mutations in AML have dual implications: the p. Gly332_Ala336del variant enhances chemosensitivity, while ARID1B dysfunction broadly facilitates an immune- evasive phenotype, likely through VISTA-mediated suppression.

This study identifies ARID1B mutation as a conditional prognostic marker and a correlate of the AML immune landscape, thereby supporting mutation-subtype-specific management and therapeutic targeting of the VISTA pathway.