Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications.

Blood
F TholMichael Heuser

Abstract

Mutations in the cohesin complex are novel, genetic lesions in acute myeloid leukemia (AML) that are not well characterized. In this study, we analyzed the frequency, clinical, and prognostic implications of mutations in STAG1, STAG2, SMC1A, SMC3, and RAD21, all members of the cohesin complex, in a cohort of 389 uniformly treated AML patients by next generation sequencing. We identified a total of 23 patients (5.9%) with somatic mutations in 1 of the cohesin genes. All gene mutations were mutually exclusive, and STAG1 (1.8%), STAG2 (1.3%), and SMC3 (1.3%) were most frequently mutated. Patients with any cohesin complex mutation had lower BAALC expression levels. We found a strong association between mutations affecting the cohesin complex and NPM1. Mutated allele frequencies were similar between NPM1 and cohesin gene mutations. Overall survival (OS), relapse-free survival (RFS), and complete remission rates (CR) were not influenced by the presence of cohesin mutations (OS: hazard ratio [HR] 0.98; 95% confidence interval [CI], 0.56-1.72 [P = .94]; RFS: HR 0.7; 95% CI, 0.36-1.38 [P = .3]; CR: mutated 83% vs wild-type 76% [P = .45]). The cohesin complex presents a novel pathway affected by recurrent mutations in AML. This study is ...Continue Reading

References

Oct 24, 2002·Blood·Sahar Barjesteh van Waalwijk van Doorn-KhosrovaniRuud Delwel
Dec 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce D ChesonUNKNOWN International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards
Jan 17, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stefan FröhlingKonstanze Döhner
Jun 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guido MarcucciUNKNOWN Cancer and Leukemia Group B Study
Jul 25, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Claudia D BaldusWolf K Hofmann
Feb 1, 2008·Nature·Kerstin S WendtJan-Michael Peters
Feb 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Thomas D BarberPhilip Hieter
May 3, 2008·The New England Journal of Medicine·Richard F SchlenkUNKNOWN German-Austrian Acute Myeloid Leukemia Study Group
Apr 24, 2009·Journal of Cell Science·Jordanka Zlatanova, Paola Caiafa
Jun 23, 2009·Genome Research·Martin KrzywinskiMarco A Marra
Dec 30, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Frederik DammJürgen Krauter
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Mar 12, 2010·Genome Research·Dominic SchmidtDuncan T Odom
Apr 7, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Katharina WagnerJürgen Krauter
Jan 6, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Frederik DammMichael Heuser
Jun 15, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Felicitas TholMichael Heuser
Sep 13, 2011·Nature·Kenichi YoshidaSeishi Ogawa
Mar 16, 2012·The New England Journal of Medicine·Matthew J WalterTimothy A Graubert
Jul 24, 2012·Cell·John S WelchRichard K Wilson
Sep 7, 2012·The Journal of Biological Chemistry·Bum-Kyu Lee, Vishwanath R Iyer
Nov 10, 2012·Nucleus·Jennifer L Gerton
Dec 12, 2012·Current Opinion in Cell Biology·Silvia Remeseiro, Ana Losada
May 3, 2013·The New England Journal of Medicine·UNKNOWN Cancer Genome Atlas Research NetworkGreg Eley
May 25, 2013·Blood·Jan KrönkeKonstanze Döhner
Jul 25, 2013·The Application of Clinical Genetics·José L Barbero

❮ Previous
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Citations

Oct 15, 2014·Seminars in Hematology·Matias SanchezRaajit Rampal
Oct 15, 2014·Seminars in Hematology·Ashley M Perry, Eyal C Attar
Oct 15, 2014·Seminars in Hematology·Luca MazzarellaPier Giuseppe Pelicci
Dec 10, 2015·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Marco Raffaele Cosenza, Alwin Krämer
Jan 9, 2015·Drug Metabolism Reviews·Lisa Pleyer, Richard Greil
Aug 31, 2014·Journal of Molecular Biology·Jörg SchönheitFrank Rosenbauer
Mar 5, 2016·Surgical Pathology Clinics·Valentina Nardi, Robert P Hasserjian
Sep 8, 2015·Current Opinion in Cell Biology·Vijay Pratap Singh, Jennifer L Gerton
Dec 8, 2015·Cell Stem Cell·Mark S Williams, Tim C P Somervaille
Jun 7, 2014·Experimental Hematology & Oncology·Bryony LeekeJulia A Horsfield
Oct 7, 2015·The Journal of Experimental Medicine·Aaron D VinyRoss L Levine
Oct 7, 2015·The Journal of Experimental Medicine·Jasper MullendersIannis Aifantis
Dec 17, 2014·Immunological Reviews·Brittany A Woods, Ross L Levine
Dec 17, 2014·Immunological Reviews·Erika L MoenLucy A Godley
May 27, 2014·BMB Reports·David A SolomonTodd Waldman
Jun 30, 2015·Experimental Hematology·Anna ErikssonSören Lehmann
Jul 19, 2015·Blood·Tanja A Gruber, James R Downing
May 3, 2015·Current Hematologic Malignancy Reports·Frank C Kuo, Fei Dong
Dec 30, 2014·Biochimica Et Biophysica Acta·Jisha AntonyJulia A Horsfield
Jul 10, 2014·Blood·Swapna ThotaJaroslaw P Maciejewski
May 22, 2016·Biochimica Et Biophysica Acta·Victoria K HillTodd Waldman
Mar 17, 2016·Blood·Nicolas DuployezClaude Preudhomme
Jun 25, 2016·The Journal of Molecular Diagnostics : JMD·Michael J KlukFrank C Kuo
Aug 21, 2016·Mutation Research. Reviews in Mutation Research·Bani Bandana Ganguly, N N Kadam
Mar 25, 2016·Journal of Clinical Pathology·Benedict YanLiang Piu Koh
Oct 18, 2016·Applied Immunohistochemistry & Molecular Morphology : AIMM·Heli RepoPauliina Kronqvist
Nov 1, 2016·International Journal of Hematology·Claire Mazumdar, Ravindra Majeti
Apr 9, 2017·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Nicolaus KrögerMichael Heuser
Mar 13, 2014·Current Hematologic Malignancy Reports·Mohamad K Khasawneh, Omar Abdel-Wahab
Jul 29, 2017·Birth Defects Research·Grazia FazioValentina Massa
Mar 16, 2018·Future Oncology·Guillermo Montalban-Bravo, Courtney D DiNardo
Apr 28, 2018·Current Opinion in Hematology·Sergi Cuartero, Matthias Merkenschlager
Apr 27, 2018·Current Opinion in Hematology·Roman Galeev, Jonas Larsson
Nov 3, 2017·Leukemia & Lymphoma·Shannon R McCurdy, Mark J Levis
Mar 2, 2018·Leukemia·Christopher Maximilian ArendsFrederik Damm

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