BCOR and BCORL1 Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target Genes

BCOR 和 BCORL1 突变通过分离 PRC1.1 与靶基因来驱动表观遗传重编程和致癌信号

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作者:Eva J Schaefer, Helen C Wang, Hannah Q Karp, Clifford A Meyer, Paloma Cejas, Micah D Gearhart, Emmalee R Adelman, Iman Fares, Annie Apffel, Klothilda Lim, Yingtian Xie, Christopher J Gibson, Monica Schenone, H Moses Murdock, Eunice S Wang, Lukasz P Gondek, Martin P Carroll, Rahul S Vedula, Eric S Wi

Significance

We demonstrate that BCOR and BCORL1 mutations in leukemia unlink PRC1.1 repressive function from target genes, resulting in epigenetic reprogramming and activation of aberrant cell signaling programs that mediate treatment resistance. Our study provides mechanistic insights into the pathogenesis of PRC1.1-mutated leukemia that inform novel therapeutic approaches. This article is highlighted in the In This Issue feature, p. 85.

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