Clinical effect of point mutations in myelodysplastic syndromes.
Rafael Bejar,Kristen E. Stevenson,Omar Abdel-Wahab,Naomi Galili,Björn Nilsson,Guillermo Garcia-Manero,Hagop M. Kantarjian,Azra Raza,Ross L. Levine,Donna Neuberg,Benjamin L. Ebert +10 more
Reads0
Chats0
TLDR
Mutations in TP53, EZH2, ETV6, RUNX1, and ASXL1 are predictors of poor overall survival in patients with myelodysplastic syndromes, independently of established risk factors.Abstract:
Background Myelodysplastic syndromes are clinically heterogeneous disorders characterized by clonal hematopoiesis, impaired differentiation, peripheral-blood cytopenias, and a risk of progression to acute myeloid leukemia. Somatic mutations may influence the clinical phenotype but are not included in current prognostic scoring systems. Methods We used a combination of genomic approaches, including next-generation sequencing and mass spectrometry–based genotyping, to identify mutations in samples of bone marrow aspirate from 439 patients with myelodysplastic syndromes. We then examined whether the mutation status for each gene was associated with clinical variables, including specific cytopenias, the proportion of blasts, and overall survival. Results We identified somatic mutations in 18 genes, including two, ETV6 and GNAS, that have not been reported to be mutated in patients with myelodysplastic syndromes. A total of 51% of all patients had at least one point mutation, including 52% of the patients with...read more
Citations
More filters
Book
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
TL;DR: Thank you very much for reading who classification of tumours of haematopoietic and lymphoid tissues, and maybe you have knowledge that, people have look hundreds of times for their chosen readings like this, but end up in malicious downloads.
Journal ArticleDOI
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia
Daniel A. Arber,Attilio Orazi,Robert P. Hasserjian,Jürgen Thiele,Michael J. Borowitz,Michelle M. Le Beau,Clara D. Bloomfield,Mario Cazzola,James W. Vardiman +8 more
TL;DR: The 2016 edition of the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition.
Journal ArticleDOI
Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
Hartmut Döhner,Elihu H. Estey,David Grimwade,Sergio Amadori,Frederick R. Appelbaum,Thomas Büchner,Hervé Dombret,Benjamin L. Ebert,Pierre Fenaux,Richard A. Larson,Ross L. Levine,Francesco Lo-Coco,Tomoki Naoe,Dietger Niederwieser,Gert J. Ossenkoppele,Miguel A. Sanz,Jorge Sierra,Martin S. Tallman,Hwei-Fang Tien,Andrew H. Wei,Andrew H. Wei,Bob Löwenberg,Clara D. Bloomfield +22 more
TL;DR: An international panel to provide updated evidence- and expert opinion-based recommendations for diagnosis and management of acute myeloid leukemia in adults includes a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
Journal ArticleDOI
Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes
Siddhartha Jaiswal,Pierre Fontanillas,Jason Flannick,Jason Flannick,Alisa K. Manning,Peter V. Grauman,Brenton G. Mar,Brenton G. Mar,R. Coleman Lindsley,Craig H. Mermel,Noël P. Burtt,Alejandro Chavez,John M. Higgins,Vladislav Moltchanov,Vladislav Moltchanov,Frank C. Kuo,Michael J. Kluk,Brian E. Henderson,Leena Kinnunen,Heikki A. Koistinen,Heikki A. Koistinen,Claes Ladenvall,Gad Getz,Adolfo Correa,Benjamin F. Banahan,Stacey Gabriel,Stacey Gabriel,Sekar Kathiresan,Heather M. Stringham,Mark I. McCarthy,Michael Boehnke,Jaakko Tuomilehto,Jaakko Tuomilehto,Jaakko Tuomilehto,Christopher A. Haiman,Leif Groop,Gil Atzmon,James G. Wilson,Donna Neuberg,David Altshuler,Benjamin L. Ebert +40 more
TL;DR: Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease.
Journal ArticleDOI
Revised International Prognostic Scoring System for Myelodysplastic Syndromes
Peter L. Greenberg,Heinz Tuechler,Julie Schanz,Guillermo Sanz,Guillermo Garcia-Manero,Francesc Solé,John M. Bennett,David T. Bowen,Pierre Fenaux,François Dreyfus,Hagop M. Kantarjian,Andrea Kuendgen,Alessandro Levis,Luca Malcovati,Mario Cazzola,Jaroslav Cermak,Christa Fonatsch,Michelle M. Le Beau,Marilyn L. Slovak,Otto Krieger,Michael Luebbert,Jaroslaw P. Maciejewski,Silvia Maria Meira Magalhães,Yasushi Miyazaki,Michael Pfeilstöcker,Mikkael A. Sekeres,Wolfgang R. Sperr,Reinhard Stauder,Sudhir Tauro,Peter Valent,Teresa Vallespi,Arjan A. van de Loosdrecht,Ulrich Germing,Detlef Haase +33 more
TL;DR: This revised IPSS-R comprehensively integrated the numerous known clinical features into a method analyzing MDS patient prognosis more precisely than the initial IPSS and should prove beneficial for predicting the clinical outcomes of untreated MDS patients and aiding design and analysis of clinical trials in this disease.
References
More filters
Journal ArticleDOI
International Scoring System for Evaluating Prognosis in Myelodysplastic Syndromes
Peter L. Greenberg,Christopher Cox,Michelle M. LeBeau,Pierre Fenaux,Pierre Morel,Guillermo Sanz,Miguel A. Sanz,Teresa Vallespi,Terry J. Hamblin,David Oscier,Kazuma Ohyashiki,Keisuke Toyama,Carlo Aul,Ghulam J. Mufti,John M. Bennett +14 more
TL;DR: The International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems as discussed by the authors.
PatentDOI
Genomic landscapes of human breast and colorectal cancers
Laura D. Wood,Williams D. Parsons,Sian Jones,Jimmy Lin,Tobias Sjöblom,Thomas D. Barber,Giovanni Parmigiani,Victor E. Velculescu,Kenneth W. Kinzler,Bert Vogelstein +9 more
TL;DR: Based on analysis of exons representing 20,857 transcripts from 18,191 genes, the authors concluded that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency.
Journal ArticleDOI
Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2
Myunggon Ko,Yun Huang,Yun Huang,Anna M. Jankowska,Utz Johann Pape,Utz Johann Pape,Mamta Tahiliani,Hozefa S. Bandukwala,Jungeun An,Jungeun An,Edward D. Lamperti,Kian Peng Koh,Rebecca D. Ganetzky,X. Shirley Liu,L. Aravind,Suneet Agarwal,Jaroslaw P. Maciejewski,Anjana Rao,Anjana Rao +18 more
TL;DR: The results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis, which may prove valuable as a diagnostic and prognostic tool to tailor therapies and assess responses to anticancer drugs.
Journal ArticleDOI
Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders
Thomas Ernst,Andrew Chase,Andrew Chase,Joannah Score,Joannah Score,Claire Hidalgo-Curtis,Claire Hidalgo-Curtis,Catherine Bryant,Catherine Bryant,Amy V. Jones,Amy V. Jones,Katherine Waghorn,Katherine Waghorn,Katerina Zoi,Fiona M. Ross,Fiona M. Ross,Andreas Reiter,Andreas Hochhaus,Hans G. Drexler,Andrew S Duncombe,Francisco Cervantes,David Oscier,Jacqueline Boultwood,Francis H. Grand,Francis H. Grand,Nicholas C.P. Cross,Nicholas C.P. Cross +26 more
TL;DR: In this article, the finding of homozygous EZH2 mutations in 9 of 12 individuals with 7q acquired uniparental disomy was described, and the mutations resulted in premature chain termination or direct abrogation of histone methyltransferase activity.
Journal ArticleDOI
High-throughput oncogene mutation profiling in human cancer
Roman K. Thomas,Alissa C. Baker,Ralph M. Debiasi,Ralph M. Debiasi,Wendy Winckler,Wendy Winckler,Thomas LaFramboise,Thomas LaFramboise,William M. Lin,William M. Lin,Meng Wang,Meng Wang,Whei Feng,Whei Feng,Thomas Zander,Laura E. MacConnaill,Laura E. MacConnaill,Jeffrey C. Lee,Jeffrey C. Lee,Rick Nicoletti,Rick Nicoletti,Charlie Hatton,Charlie Hatton,Mary Goyette,Luc Girard,Kuntal Majmudar,Liuda Ziaugra,Kwok-Kin Wong,Stacey Gabriel,Rameen Beroukhim,Rameen Beroukhim,Michael Peyton,Jordi Barretina,Jordi Barretina,Amit Dutt,Amit Dutt,Caroline Emery,Heidi Greulich,Heidi Greulich,Kinjal Shah,Kinjal Shah,Hidefumi Sasaki,Adi F. Gazdar,John D. Minna,Scott A. Armstrong,Ingo K. Mellinghoff,F. Stephen Hodi,Glenn Dranoff,Paul S. Mischel,Timothy F. Cloughesy,Stan F. Nelson,Linda M. Liau,Kirsten D. Mertz,Kirsten D. Mertz,Mark A. Rubin,Holger Moch,Massimo Loda,William J. Catalona,Jonathan A. Fletcher,Sabina Signoretti,Frederic J. Kaye,Kenneth C. Anderson,George D. Demetri,Reinhard Dummer,Stephan N. Wagner,Meenhard Herlyn,William R. Sellers,William R. Sellers,Matthew Meyerson,Matthew Meyerson,Levi A. Garraway,Levi A. Garraway +71 more
TL;DR: High-throughput genotyping is adapted to query 238 known oncogene mutations across 1,000 human tumor samples and established robust mutation distributions spanning 17 cancer types, offering a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time'.
Related Papers (5)
Revised International Prognostic Scoring System for Myelodysplastic Syndromes
Peter L. Greenberg,Heinz Tuechler,Julie Schanz,Guillermo Sanz,Guillermo Garcia-Manero,Francesc Solé,John M. Bennett,David T. Bowen,Pierre Fenaux,François Dreyfus,Hagop M. Kantarjian,Andrea Kuendgen,Alessandro Levis,Luca Malcovati,Mario Cazzola,Jaroslav Cermak,Christa Fonatsch,Michelle M. Le Beau,Marilyn L. Slovak,Otto Krieger,Michael Luebbert,Jaroslaw P. Maciejewski,Silvia Maria Meira Magalhães,Yasushi Miyazaki,Michael Pfeilstöcker,Mikkael A. Sekeres,Wolfgang R. Sperr,Reinhard Stauder,Sudhir Tauro,Peter Valent,Teresa Vallespi,Arjan A. van de Loosdrecht,Ulrich Germing,Detlef Haase +33 more
Frequent pathway mutations of splicing machinery in myelodysplasia
Kenichi Yoshida,Masashi Sanada,Yuichi Shiraishi,Daniel Nowak,Yasunobu Nagata,Ryo Yamamoto,Yusuke Sato,Aiko Sato-Otsubo,Ayana Kon,Masao Nagasaki,George Chalkidis,Yutaka Suzuki,Masashi Shiosaka,Ryoichiro Kawahata,Tomoyuki Yamaguchi,Makoto Otsu,Naoshi Obara,Mamiko Sakata-Yanagimoto,Ken Ishiyama,Hiraku Mori,Florian Nolte,Wolf-Karsten Hofmann,Shuichi Miyawaki,Sumio Sugano,Claudia Haferlach,H. Phillip Koeffler,H. Phillip Koeffler,Lee Yung Shih,Torsten Haferlach,Shigeru Chiba,Hiromitsu Nakauchi,Satoru Miyano,Seishi Ogawa +32 more
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