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DOI 10.1038/s41586-018-0623-z

Медицинская библиотека · Nature · 2018

Functional genomic landscape of acute myeloid leukaemia.

Tyner Jeffrey W, Tognon Cristina E, Bottomly Daniel, Wilmot Beth, Kurtz Stephen E, Savage Samantha L, Long Nicola, Schultz Anna Reister, Traer Elie, Abel Melissa, Agarwal Anupriya, Blucher Aurora, Borate Uma, Bryant Jade, Burke Russell, Carlos Amy, Carpenter Richie, Carroll Joseph, Chang Bill H, Coblentz Cody, d'Almeida Amanda, Cook Rachel, Danilov Alexey, Dao Kim-Hien T, Degnin Michie, Devine Deirdre, Dibb James, Edwards David K, Eide Christopher A, English Isabel, Glover Jason, Henson Rachel, Ho Hibery, Jemal Abdusebur, Johnson Kara, Johnson Ryan, Junio Brian, Kaempf Andy, Leonard Jessica, Lin Chenwei, Liu Selina Qiuying, Lo Pierrette, Loriaux Marc M, Luty Samuel, Macey Tara, MacManiman Jason, Martinez Jacqueline, Mori Motomi, Nelson Dylan, Nichols Ceilidh, Peters Jill, Ramsdill Justin, Rofelty Angela, Schuff Robert, Searles Robert, Segerdell Erik, Smith Rebecca L, Spurgeon Stephen E, Sweeney Tyler, Thapa Aashis, Visser Corinne, Wagner Jake, Watanabe-Smith Kevin, Werth Kristen, Wolf Joelle, White Libbey, Yates Amy, Zhang Haijiao, Cogle Christopher R, Collins Robert H, Connolly Denise C, Deininger Michael W, Drusbosky Leylah, Hourigan Christopher S, Jordan Craig T, Kropf Patricia, Lin Tara L, Martinez Micaela E, Medeiros Bruno C, Pallapati Rachel R, Pollyea Daniel A, Swords Ronan T, Watts Justin M, Weir Scott J, Wiest David L, Winters Ryan M, McWeeney Shannon K, Druker Brian J

Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset-accessible through the Beat AML data viewer (Vizome)-that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.

Для цитирования: Tyner Jeffrey W, Tognon Cristina E, Bottomly Daniel, Wilmot Beth, Kurtz Stephen E, Savage Samantha L, Long Nicola, Schultz Anna Reister, Traer Elie, Abel Melissa, Agarwal Anupriya, Blucher Aurora, Borate Uma, Bryant Jade, Burke Russell, Carlos Amy, Carpenter Richie, Carroll Joseph, Chang Bill H, Coblentz Cody, d'Almeida Amanda, Cook Rachel, Danilov Alexey, Dao Kim-Hien T, Degnin Michie, Devine Deirdre, Dibb James, Edwards David K, Eide Christopher A, English Isabel, Glover Jason, Henson Rachel, Ho Hibery, Jemal Abdusebur, Johnson Kara, Johnson Ryan, Junio Brian, Kaempf Andy, Leonard Jessica, Lin Chenwei, Liu Selina Qiuying, Lo Pierrette, Loriaux Marc M, Luty Samuel, Macey Tara, MacManiman Jason, Martinez Jacqueline, Mori Motomi, Nelson Dylan, Nichols Ceilidh, Peters Jill, Ramsdill Justin, Rofelty Angela, Schuff Robert, Searles Robert, Segerdell Erik, Smith Rebecca L, Spurgeon Stephen E, Sweeney Tyler, Thapa Aashis, Visser Corinne, Wagner Jake, Watanabe-Smith Kevin, Werth Kristen, Wolf Joelle, White Libbey, Yates Amy, Zhang Haijiao, Cogle Christopher R, Collins Robert H, Connolly Denise C, Deininger Michael W, Drusbosky Leylah, Hourigan Christopher S, Jordan Craig T, Kropf Patricia, Lin Tara L, Martinez Micaela E, Medeiros Bruno C, Pallapati Rachel R, Pollyea Daniel A, Swords Ronan T, Watts Justin M, Weir Scott J, Wiest David L, Winters Ryan M, McWeeney Shannon K, Druker Brian J. Functional genomic landscape of acute myeloid leukaemia.. Nature. 2018. DOI: 10.1038/s41586-018-0623-z.

Предметные рубрики MeSH

Core Binding Factor Alpha 2 SubunitDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADatasets as TopicExomeFemaleGene Expression Regulation, NeoplasticGenome, HumanGenomicsHumansLeukemia, Myeloid, AcuteMaleMolecular Targeted TherapyNuclear ProteinsNucleophosminProto-Oncogene ProteinsRepressor ProteinsSequence Analysis, RNASerine-Arginine Splicing Factors
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