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2篇 您的检索式:作者名="Ilene Galinsky"
    题名 作者 年代 出处 被引量
1Vulnerabilities in mIDH2 AML confer sensitivity to APL-like targeted combination therapy显示文摘Although targeted therapies have proven effective and even curative in human leukaemia, resistance often ensues. IDH enzymes are mutated in ~20% of human AML, with targeted therapies under clinical evaluation. We here characterize leukaemia evolution from mutant IDH2 (mIDH2)-dependence to independence identifying key targetable vulnerabilities of mIDH2 leukaemia that are retained during evolution and progression from early to late stages. Mechanistically, we find that mIDH2 leukaemia are metastable and vulnerable at two distinct levels. On the one hand, they are characterized by oxidative and genotoxic stress, in spite of increased 1-carbon metabolism and glutathione levels. On the other hand, mIDH2 leukaemia display inhibition of LSD1 and a resulting transcriptional signature of all-trans retinoic acid (ATRA) sensitization, in spite of a state of suppressed ATRA signalling due to increased levels of PIN1. We further identify GSH/ROS and PIN1/LSD1 as critical nodes for leukaemia maintenance and the combination of ATRA and arsenic trioxide (ATO) as a key therapeutic modality to target these vulnerabilities. Strikingly, we demonstrate that the combination of ATRA and ATO proves to be a powerfully synergistic and effective therapy in a number of mouse and human mIDH1/2 leukemic models. Thus, our findings pave the way towards the treatment of a sizable fraction of human AMLs through targeted APL-like combinatorial therapies.Vera Mugoni Riccardo Panella Giulia Cheloni Ming Chen Olga Pozdnyakova Dina Stroopinsky Jlenia Guarnerio Emanuele Monteleone Jonathan David Lee Lourdes Mendez Archita Venugopal Menon Jon Christopher Aster Andrew A. Lane Richard Maury Stone Ilene Galinsky José Cervera Zamora Francesco Lo-Coco Manoj Kumar Bhasin David Avigan Letizia Longo John Gerard Clohessy Pier Paolo Pandolfi 2019Cell Research2019,29,6:1
2The intersection of genetic and chemical genomic screens identifies GSK-3[alpha] as a target in human acute myeloid leukemia显示文摘Banerji Versha Frumm Stacey M Ross Kenneth N Li Loretta S Schinzel Anna C Hahn Cynthia K Kakoza Rose M Chow Kwan T Ross Linda Alexe Gabriela Tolliday Nicola Inguilizian Haig Galinsky Ilene Stone Richard M DeAngelo Daniel J Roti Giovanni As 2012EN2012,,3:1
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