MBP1 inhibits AML proliferation through downregulating noncanonical Wnt/Ca2+ signaling pathway.

Acute myeloid leukemia (AML) remains therapeutically challenging, highlighting an urgent need for novel therapeutic targets. Our prior work showed ENO1 promotes AML, but the role of its short variant MBP1 was unknown. Here, we demonstrated significant downregulation of MBP1 alongside ENO1 upregulation in primary AML patient samples compared to healthy donors, establishing an imbalanced ENO1/MBP1 ratio. Functionally, restoring MBP1 expression in AML cell lines (KG1, OCI-AML3) inhibited cell proliferation, suppressed colony formation, induced cell apoptosis, and triggered G1-phase cell cycle arrest in vitro. Mechanistically, RNA-seq and pathway analysis revealed that MBP1 overexpression suppresses the non-canonical Wnt/Ca2+ signaling pathway by downregulating its key components Wnt11 and NFATc1. Crucially, in vivo studies using NSG mouse xenografts confirmed that MBP1 overexpression significantly attenuated AML progression, reducing tumor burden in spleen and bone marrow. These results demonstrate that MBP1 deficiency promotes AML via Wnt11/NFATc1 activation, revealing a promising therapeutic target.