YY1 Knockdown Relieves the Differentiation Block and Restores Apoptosis in AML Cells

YY1 敲低可缓解 AML 细胞分化阻滞并恢复细胞凋亡

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作者:Nelida Ines Noguera, Serena Travaglini, Stefania Scalea, Caterina Catalanotto, Anna Reale, Michele Zampieri, Alessandra Zaza, Maria Rosaria Ricciardi, Daniela Francesca Angelini, Agostino Tafuri, Tiziana Ottone, Maria Teresa Voso, Giuseppe Zardo

Abstract

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.

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