Effect of knockdown PHF8 on the transcriptional regulation of BCR-ABL1 fusion gene on CML cell line K562

Epigenetic dysregulation plays a vital role in the pathogenesis of hematological malignancies. Histone demethylation is a key mechanism for epigenetic modification, of which dysregulation has an immeasurable effect on both TKI resistance and the transformation from CP CML to AP/BC CML. Here we report that PHF8 regulate the transcription of the driven fusion gene BCR-ABL1 in CML cells. The depletion of PHF8 promotes differentiation and inhibits proliferation. Furthermore, the proliferation-inhibited function of PHF8-knockdown have stronger effect on imatinib mesylate (IM)-resistant CML cells. We identified that PHF8 as a transcriptional modulator interacted with the promoter of the BCR::ABL1 fusion gene and alters the methylation levels of H3K9me1, H3K9me2 and H3K27me1, thereby promoting BCR::ABL1 transcription. Taken together, PHF8, as an oncogenic protein, was abnormally expressed in CML, altered the histone methylation levels of BCR::ABL1 promoter, and upregulated BCR::ABL1. Our study indicated that regulating histone demethylation is essential for BCR::ABL1 expression. Targeting PHF8 can be a promising therapeutic option for CML patients with TKI resistance.