Journal ArticleDOI
Acute myeloid leukaemia in adults
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TLDR
The goal is to target the molecular abnormalities identified at diagnosis; however, several aberrations can coexist in subclones of acute myeloid leukaemia, making the disease less likely to be inhibited by a single agent.About:
This article is published in The Lancet.The article was published on 2013-02-09. It has received 472 citations till now. The article focuses on the topics: Myeloid & Transplantation.read more
Citations
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Journal ArticleDOI
A 17-gene stemness score for rapid determination of risk in acute leukaemia
Stanley W.K. Ng,Amanda Mitchell,James A. Kennedy,James A. Kennedy,James A. Kennedy,Weihsu C. Chen,Jessica McLeod,Narmin Ibrahimova,Andrea Arruda,Andreea C. Popescu,Vikas Gupta,Vikas Gupta,Vikas Gupta,Aaron D. Schimmer,Andre C. Schuh,Andre C. Schuh,Andre C. Schuh,Karen W.L. Yee,Karen W.L. Yee,Karen W.L. Yee,Lars Bullinger,Tobias Herold,Tobias Herold,Dennis Görlich,Thomas Büchner,Wolfgang Hiddemann,Wolfgang Hiddemann,Wolfgang E. Berdel,Bernhard Wörmann,Meyling Cheok,Claude Preudhomme,Hervé Dombret,Klaus H. Metzeler,Klaus H. Metzeler,Christian Buske,Bob Löwenberg,Peter J. M. Valk,Peter W. Zandstra,Mark D. Minden,John E. Dick,John E. Dick,Jean C.Y. Wang,Jean C.Y. Wang,Jean C.Y. Wang +43 more
TL;DR: The LSC17 score provides clinicians with a rapid and powerful tool to identify AML patients who do not benefit from standard therapy and who should be enrolled in trials evaluating novel upfront or post-remission strategies.
Journal ArticleDOI
A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia
Konstantinos Tzelepis,Hiroko Koike-Yusa,Etienne De Braekeleer,Yang Li,Emmanouil Metzakopian,Oliver M. Dovey,Annalisa Mupo,Vera V. Grinkevich,Meng Li,Milena Mazan,Malgorzata Gozdecka,Shuhei Ohnishi,Jonathan L. Cooper,Miten Patel,Thomas McKerrell,Bin Chen,Ana Domingues,Paolo Gallipoli,Sarah A. Teichmann,Hannes Ponstingl,Ultan McDermott,Julio Saez-Rodriguez,Julio Saez-Rodriguez,Brian J. P. Huntly,Francesco Iorio,Cristina Pina,George S. Vassiliou,George S. Vassiliou,Kosuke Yusa +28 more
TL;DR: KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells.
Journal ArticleDOI
Acute Myelogenous Leukemia-Induced Sympathetic Neuropathy Promotes Malignancy in an Altered Hematopoietic Stem Cell Niche
Maher Hanoun,Dachuan Zhang,Toshihide Mizoguchi,Sandra Pinho,Halley Pierce,Yuya Kunisaki,Julie Lacombe,Scott A. Armstrong,Ulrich Dührsen,Paul S. Frenette +9 more
TL;DR: It is found that neuropathy of the sympathetic nervous system (SNS) promotes leukemic bone marrow infiltration in an MLL-AF9 AML model, indicating that sympathetic neuropathy may represent a mechanism for the malignancy in order to co-opt the microenvironment and suggesting separate mesenchymal niche activities for malignant and healthy hematopoietic stem cells in the bone marrow.
Journal ArticleDOI
Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia.
Bas J. Wouters,Ruud Delwel +1 more
TL;DR: An overview of the current state of epigenetics and epigenetic therapy in AML is provided and perspectives on how to identify promising new approaches for epigenetic targeted treatment are described.
Journal ArticleDOI
Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion
Anna M. Paczulla,Kathrin Rothfelder,Simon Raffel,Simon Raffel,Martina Konantz,Julia Steinbacher,Hui Wang,Claudia Tandler,Marcelle Ndoh Mbarga,Thorsten Schaefer,Mattia Falcone,Eva Nievergall,Daniela Dörfel,Pauline Hanns,Jakob Passweg,Christoph Lutz,Juerg Schwaller,Robert Zeiser,Bruce R. Blazar,Michael A. Caligiuri,Stephan Dirnhofer,Pontus Lundberg,Lothar Kanz,Leticia Quintanilla-Martinez,Alexander Steinle,Andreas Trumpp,Helmut R. Salih,Claudia Lengerke +27 more
TL;DR: It is demonstrated that stemness and immune evasion are closely intertwined in AML and a strong rationale for targeting therapy-resistant LSCs by PARP1 inhibition, which renders them amenable to control by NK cells in vivo is provided.
References
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The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
James W. Vardiman,Juergen Thiele,Daniel A. Arber,Richard D. Brunning,Michael J. Borowitz,Anna Porwit,Nancy L. Harris,Michelle M. Le Beau,Eva Hellström-Lindberg,Ayalew Tefferi,Clara D. Bloomfield +10 more
TL;DR: The classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.
Journal ArticleDOI
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet.
Hartmut Döhner,Elihu H. Estey,Sergio Amadori,Frederick R. Appelbaum,Thomas Büchner,Alan Kenneth Burnett,Hervé Dombret,Pierre Fenaux,David Grimwade,Richard A. Larson,Francesco Lo-Coco,Tomoki Naoe,Dietger Niederwieser,Gert J. Ossenkoppele,Miguel A. Sanz,Jorge Sierra,Martin S. Tallman,Bob Löwenberg,Clara D. Bloomfield +18 more
TL;DR: An international expert panel is provided to provide updated evidence- and expert opinion-based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials.
Journal ArticleDOI
Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia
Bruce D. Cheson,John M. Bennett,Kenneth J. Kopecky,Thomas Büchner,Cheryl L. Willman,Elihu H. Estey,Charles A. Schiffer,Hartmut Doehner,Martin S. Tallman,T. Andrew Lister,Francesco Lo-Coco,Roel Willemze,Andrea Biondi,Wolfgang Hiddemann,Richard A. Larson,Bob Löwenberg,Miguel A. Sanz,David R. Head,Ryuzo Ohno,Clara D. Bloomfield +19 more
TL;DR: An International Working Group met to revise the diagnostic and response criteria for acute myelogenous leukemia originally published in 1990, as well as to provide definitions of outcomes and reporting standards to improve interpretability of data and comparisons among trials as mentioned in this paper.
Journal ArticleDOI
Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.
Pierre Fenaux,Ghulam J. Mufti,Eva Hellström-Lindberg,Valeria Santini,Carlo Finelli,Aristoteles Giagounidis,Robert Schoch,Norbert Gattermann,Guillermo Sanz,Alan F. List,Steven D. Gore,John F. Seymour,John M. Bennett,John C. Byrd,Jay Backstrom,Linda Zimmerman,David McKenzie,C.L. Beach,Lewis R. Silverman +18 more
TL;DR: Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care.
Journal ArticleDOI
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
Li Ding,Timothy J. Ley,David E. Larson,Christopher A. Miller,Daniel C. Koboldt,John S. Welch,Julie Ritchey,Margaret A. Young,Tamara Lamprecht,Michael D. McLellan,Joshua F. McMichael,John W. Wallis,Charles Lu,Dong Shen,Chris Harris,David J. Dooling,Robert S. Fulton,Lucinda Fulton,Ken Chen,Heather Schmidt,Joelle Kalicki-Veizer,Vincent Magrini,Lisa Cook,Sean McGrath,Tammi L. Vickery,Michael C. Wendl,Sharon Heath,Mark A. Watson,Daniel C. Link,Michael H. Tomasson,William D. Shannon,Jacqueline E. Payton,Shashikant Kulkarni,Peter Westervelt,Matthew J. Walter,Timothy A. Graubert,Elaine R. Mardis,Richard K. Wilson,John F. DiPersio +38 more
TL;DR: The sequenced primary tumour and relapse genomes from eight AML patients and validated hundreds of somatic mutations using deep sequencing demonstrated that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped by the chemotherapy that the patients receive to establish and maintain remissions.
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