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TP53 Mutation Status Divides Myelodysplastic Syndromes with Complex Karyotypes into Distinct Prognostic Subgroups

dc.contributor.authorSavona, Michael R.
dc.contributor.authorSeegmiller, Adam
dc.identifier.citationHaase D, Stevenson KE, Neuberg D, et al. TP53 mutationstatus divides myelodysplastic syndromes with complexkaryotypes into distinct prognostic subgroups. Leukemia.2019;doi: 10.1038/s41375-018-0351-2.en_US
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at
dc.description.abstractRisk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p < 0.005), monosomal karyotype (p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities (p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (> 10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features.en_US
dc.description.sponsorshipWe would like to thank the MDS Foundation for their support of the International Working Group for MDS and Celgene for funding the efforts of the IWG-prognosis molecular subcommittee and this study. RB was additionally supported by K08 DK091360. PV acknowledges funding from the MRC Disease Team Awards (G1000729/94931 and MR/L008963/1) MRC Molecular Haematology Unit and the Oxford Partnership Comprehensive Biomedical Research Centre (NIHR BRC Funding scheme. oxfbrc-2012-1). LQ is funded by an MRC Clinician Scientist Fellowship. JB and AP acknowledge funding from Bloodwise (UK). LM acknowledges funding from Associazione Italiana per la Ricerca sul Cancro (AIRC, Individual Grant 20125). MH acknowledges funding from DFG grant HE 5240/6-1. In addition, we would like to thank the following for their help with this study: Jin Shao from Washington University in St. Louis, USA; Professor Mathilde Hunault-Berger from CHU Angers, France; Professor Norbert Vey from Institut Paoli Calmettes, Marseille, France; Michael Byrne, P Brent Ferrell, David R Head, Ridas Juskevicius, Carrie Kitko, Emily F Mason, Sanjay R Mohan, Claudio A Mosse, Tamara K Moyo, Aaron C Shaver, Andrew L Sochacki, and Stephen A Strickland from Vanderbilt University.en_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
dc.subjectacute myeloid-leukemiaen_US
dc.subjectstem-cell transplantationen_US
dc.subjectdriver somatic mutationsen_US
dc.subjectmonosomal karyotypeen_US
dc.subjectscoring systemen_US
dc.subjectallele burdenen_US
dc.subject.lcshAcute myeloid leukemiaen_US
dc.subject.lcshStem Cell Transplantationen_US
dc.titleTP53 Mutation Status Divides Myelodysplastic Syndromes with Complex Karyotypes into Distinct Prognostic Subgroupsen_US

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