In this study we analyzed the expression of Yin and Yang 1 protein (YY1), a member of the noncanonical PcG complexes, in AML patient samples and AML cell lines and the effect of YY1 downregulation on the AML differentiation block. Our results show that YY1 is significantly overexpressed in AML patient samples and AML cell lines and that YY1 knockdown relieves the differentiation block. YY1 downregulation in two AML cell lines (HL-60 and OCI-AML3) and one AML patient sample restored the expression of members of the CEBP protein family, increased the expression of extrinsic growth factors/receptors and surface antigenic markers, induced morphological cell characteristics typical of myeloid differentiation, and sensitized cells to retinoic acid treatment and to apoptosis. Overall, our data show that YY1 is not a secondary regulator of myeloid differentiation but that, if overexpressed, it can play a predominant role in myeloid differentiation block.
本研究分析了急性髓系白血病(AML)患者样本及细胞系中非典型PcG复合体成员Yin Yang 1蛋白(YY1)的表达情况,以及YY1下调对AML分化阻滞的影响。结果表明,YY1在AML患者样本及细胞系中显著过表达,而YY1敲低可缓解分化阻滞。在两种AML细胞系(HL-60和OCI-AML3)及一例AML患者样本中下调YY1表达,能恢复CEBP蛋白家族成员的表达,增加外源性生长因子/受体及表面抗原标志物的表达,诱导髓系分化典型的细胞形态特征,并增强细胞对视黄酸治疗及凋亡的敏感性。总体而言,我们的数据表明YY1并非髓系分化的次要调节因子,若出现过表达,它可在髓系分化阻滞中发挥主导作用。
YY1 Knockdown Relieves the Differentiation Block and Restores Apoptosis in AML Cells