Clinic
therapy of
acute myeloid leukemia (AML) remains unsatisfactory that urges for development of novel strategies. Recent studies identified ANP32A as a novel
biomarker of unfavorable outcome of
leukemia, which promoted leukemogenesis by increasing H3 acetylation and the expression of lipid metabolism genes. It is of great significance to investigate whether targeting ANP32A is a novel strategy for
leukemia therapy. To target ANP32A, we identified a
peptide that competed with ANP32A to bind to
histone 3 (termed as H3-binding
peptide, H3BP). Disrupting ANP32A and H3 interaction by the overexpression of H3BP-GFP fusion
protein mimicked the effect of ANP32A knockdown, impaired H3 acetylation on multiple locus of target genes, reduced proliferation, and caused apoptosis in
leukemia cells. Furthermore, a synthesized membrane-penetrating
peptide TAT-H3BP effectively entered into
leukemia cells and phenocopied such effect. In vivo, TAT-H3BP showed potent efficacy against
leukemia: Intra-
tumor injection of TAT-H3BP significantly reduced the volume of subcutaneous
tumors in nude mice and recipient mice engrafted with TAT-H3BP-pretreated 6133/MPL W515L cells exhibited ameliorated
leukemia burden and prolonged survival. Noticeably, TAT-H3BP efficiently suppressed proliferation and colony-forming unit of human primary AML cells without affecting normal cord blood cells. Our findings demonstrate that intervening the physical interaction of ANP32A with H3 impairs the oncogenicity of ANP32A and may be a promising therapeutic strategy against AML.