Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia.

Abstract

Clinical significance of plant homeodomain finger 2 (PHF2) expressions is explored in acute lymphoblastic leukemia (ALL) patients. mRNA level was examined by qPCR. The retroviral gene expression, shRNA knockdown and chromatin-immunoprecipitation are used to observe IKAROS regulation on PHF2 transcription. PHF2 expression is significantly reduced in subsets of ALL patients, and PHF2 low expression correlates with leukemia cell proliferation and an elevation of several poor prognostic markers in B-cell ALL. IKAROS directly promotes PHF2 expression and patients with IKAROS deletion have significantly lower PHF2 expression. Casein kinase II (CK2) inhibitor significantly promotes PHF2 expression in an IKAROS-dependent manner, and casein kinase II inhibitor treatment also results in an increase of PHF2 expression and enrichment of IKAROS and H3K4me3 at PHF2 promoter in primary cells. Our results demonstrate that the IKAROS promotes PHF2 expression, and suggest that PHF2 low expression works with the IKAROS gene deletion to drive oncogenesis of ALL.