Cell
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CKIα ablation induces p53 activation, and CKIα degradation underlies the therapeutic effect of lenalidomide in a pre-leukemia syndrome. Here we describe the development of CKIα inhibitors, which co-target the transcriptional kinases CDK7 and CDK9, thereby augmenting CKIα-induced p53 activation and its anti-leukemic activity. ⋯ We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. Leukemia progenitors are selectively eliminated by the inhibitors, explaining their therapeutic efficacy with preserved hematopoiesis and leukemia cure potential; they eradicate leukemia in MLL-AF9 and Tet2-/-;Flt3ITD AML mouse models and in several patient-derived AML xenograft models, supporting their potential efficacy in curing human leukemia.
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Biography Historical Article
Histone Modifications: Insights into Their Influence on Gene Expression.
This year's Albert Lasker Basic Medical Research Award honors David Allis and Michael Grunstein for their pioneering research that highlighted the importance of histones and their post-translational modifications in the direct control of gene expression.
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Joan Steitz radiates a passion for science. Whether she's teaching an undergraduate course, mentoring a grad student or post-doc, or speaking at a scientific conference, her enthusiasm and curiosity for all things RNA is infectious. Joan, the recipient of the 2018 Lasker-Koshland Special Achievement Award in Medical Science, spoke with Cell editor (and her former post-doc) Lara Szewczak about how she came to be an advocate for women in science and shared advice for young scientists entering the research community today. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.
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Together with David Allis, Michael Grunstein just received the Lasker Basic Medical research award. The article that follows is a transcript of a conversation with Jacques Deguine, scientific editor at Cell, that was edited for length. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.