Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation
Identifieur interne : 000264 ( Main/Exploration ); précédent : 000263; suivant : 000265Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation
Auteurs : R. C. Lindsley ; W. Saber ; B. G. Mar ; R. Redd ; T. Wang ; M. D. Haagenson ; P. V. Grauman ; Z.-H. Hu ; S. R. Spellman ; S. J. Lee ; M. R. Verneris ; K. Hsu ; K. Fleischhauer ; C. Cutler ; J. H. Antin ; D. Neuberg ; B. L. EbertSource :
- The New England journal of medicine [ 0028-4793 ] ; 2017.
Abstract
Genetic mutations drive the pathogenesis of the myelodysplastic syndrome (MDS) and are closely associated with clinical phenotype. Therefore, genetic mutations may predict clinical outcomes after allogeneic hematopoietic stem-cell transplantation.
We performed targeted mutational analysis on samples obtained before transplantation from 1514 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research Repository between 2005 and 2014. We evaluated the association of mutations with transplantation outcomes, including overall survival, relapse, and death without relapse.
Genetic profiling revealed that molecular subgroups of patients undergoing allogeneic hematopoietic stem-cell transplantation for MDS may inform prognostic stratification and the selection of conditioning regimen. (Funded by the Edward P. Evans Foundation and others.)
Url:
DOI: 10.1056/NEJMoa1611604
PubMed: 28177873
PubMed Central: 5438571
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 003291
- to stream Pmc, to step Curation: 003290
- to stream Pmc, to step Checkpoint: 000126
- to stream Ncbi, to step Merge: 008D03
- to stream Ncbi, to step Curation: 008D03
- to stream Ncbi, to step Checkpoint: 008D03
- to stream Main, to step Merge: 000264
- to stream Main, to step Curation: 000264
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation</title>
<author><name sortKey="Lindsley, R C" sort="Lindsley, R C" uniqKey="Lindsley R" first="R. C." last="Lindsley">R. C. Lindsley</name>
</author>
<author><name sortKey="Saber, W" sort="Saber, W" uniqKey="Saber W" first="W." last="Saber">W. Saber</name>
</author>
<author><name sortKey="Mar, B G" sort="Mar, B G" uniqKey="Mar B" first="B. G." last="Mar">B. G. Mar</name>
</author>
<author><name sortKey="Redd, R" sort="Redd, R" uniqKey="Redd R" first="R." last="Redd">R. Redd</name>
</author>
<author><name sortKey="Wang, T" sort="Wang, T" uniqKey="Wang T" first="T." last="Wang">T. Wang</name>
</author>
<author><name sortKey="Haagenson, M D" sort="Haagenson, M D" uniqKey="Haagenson M" first="M. D." last="Haagenson">M. D. Haagenson</name>
</author>
<author><name sortKey="Grauman, P V" sort="Grauman, P V" uniqKey="Grauman P" first="P. V." last="Grauman">P. V. Grauman</name>
</author>
<author><name sortKey="Hu, Z H" sort="Hu, Z H" uniqKey="Hu Z" first="Z.-H." last="Hu">Z.-H. Hu</name>
</author>
<author><name sortKey="Spellman, S R" sort="Spellman, S R" uniqKey="Spellman S" first="S. R." last="Spellman">S. R. Spellman</name>
</author>
<author><name sortKey="Lee, S J" sort="Lee, S J" uniqKey="Lee S" first="S. J." last="Lee">S. J. Lee</name>
</author>
<author><name sortKey="Verneris, M R" sort="Verneris, M R" uniqKey="Verneris M" first="M. R." last="Verneris">M. R. Verneris</name>
</author>
<author><name sortKey="Hsu, K" sort="Hsu, K" uniqKey="Hsu K" first="K." last="Hsu">K. Hsu</name>
</author>
<author><name sortKey="Fleischhauer, K" sort="Fleischhauer, K" uniqKey="Fleischhauer K" first="K." last="Fleischhauer">K. Fleischhauer</name>
</author>
<author><name sortKey="Cutler, C" sort="Cutler, C" uniqKey="Cutler C" first="C." last="Cutler">C. Cutler</name>
</author>
<author><name sortKey="Antin, J H" sort="Antin, J H" uniqKey="Antin J" first="J. H." last="Antin">J. H. Antin</name>
</author>
<author><name sortKey="Neuberg, D" sort="Neuberg, D" uniqKey="Neuberg D" first="D." last="Neuberg">D. Neuberg</name>
</author>
<author><name sortKey="Ebert, B L" sort="Ebert, B L" uniqKey="Ebert B" first="B. L." last="Ebert">B. L. Ebert</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">28177873</idno>
<idno type="pmc">5438571</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438571</idno>
<idno type="RBID">PMC:5438571</idno>
<idno type="doi">10.1056/NEJMoa1611604</idno>
<date when="2017">2017</date>
<idno type="wicri:Area/Pmc/Corpus">003291</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003291</idno>
<idno type="wicri:Area/Pmc/Curation">003290</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">003290</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000126</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000126</idno>
<idno type="wicri:Area/Ncbi/Merge">008D03</idno>
<idno type="wicri:Area/Ncbi/Curation">008D03</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">008D03</idno>
<idno type="wicri:doubleKey">0028-4793:2017:Lindsley R:prognostic:mutations:in</idno>
<idno type="wicri:Area/Main/Merge">000264</idno>
<idno type="wicri:Area/Main/Curation">000264</idno>
<idno type="wicri:Area/Main/Exploration">000264</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation</title>
<author><name sortKey="Lindsley, R C" sort="Lindsley, R C" uniqKey="Lindsley R" first="R. C." last="Lindsley">R. C. Lindsley</name>
</author>
<author><name sortKey="Saber, W" sort="Saber, W" uniqKey="Saber W" first="W." last="Saber">W. Saber</name>
</author>
<author><name sortKey="Mar, B G" sort="Mar, B G" uniqKey="Mar B" first="B. G." last="Mar">B. G. Mar</name>
</author>
<author><name sortKey="Redd, R" sort="Redd, R" uniqKey="Redd R" first="R." last="Redd">R. Redd</name>
</author>
<author><name sortKey="Wang, T" sort="Wang, T" uniqKey="Wang T" first="T." last="Wang">T. Wang</name>
</author>
<author><name sortKey="Haagenson, M D" sort="Haagenson, M D" uniqKey="Haagenson M" first="M. D." last="Haagenson">M. D. Haagenson</name>
</author>
<author><name sortKey="Grauman, P V" sort="Grauman, P V" uniqKey="Grauman P" first="P. V." last="Grauman">P. V. Grauman</name>
</author>
<author><name sortKey="Hu, Z H" sort="Hu, Z H" uniqKey="Hu Z" first="Z.-H." last="Hu">Z.-H. Hu</name>
</author>
<author><name sortKey="Spellman, S R" sort="Spellman, S R" uniqKey="Spellman S" first="S. R." last="Spellman">S. R. Spellman</name>
</author>
<author><name sortKey="Lee, S J" sort="Lee, S J" uniqKey="Lee S" first="S. J." last="Lee">S. J. Lee</name>
</author>
<author><name sortKey="Verneris, M R" sort="Verneris, M R" uniqKey="Verneris M" first="M. R." last="Verneris">M. R. Verneris</name>
</author>
<author><name sortKey="Hsu, K" sort="Hsu, K" uniqKey="Hsu K" first="K." last="Hsu">K. Hsu</name>
</author>
<author><name sortKey="Fleischhauer, K" sort="Fleischhauer, K" uniqKey="Fleischhauer K" first="K." last="Fleischhauer">K. Fleischhauer</name>
</author>
<author><name sortKey="Cutler, C" sort="Cutler, C" uniqKey="Cutler C" first="C." last="Cutler">C. Cutler</name>
</author>
<author><name sortKey="Antin, J H" sort="Antin, J H" uniqKey="Antin J" first="J. H." last="Antin">J. H. Antin</name>
</author>
<author><name sortKey="Neuberg, D" sort="Neuberg, D" uniqKey="Neuberg D" first="D." last="Neuberg">D. Neuberg</name>
</author>
<author><name sortKey="Ebert, B L" sort="Ebert, B L" uniqKey="Ebert B" first="B. L." last="Ebert">B. L. Ebert</name>
</author>
</analytic>
<series><title level="j">The New England journal of medicine</title>
<idno type="ISSN">0028-4793</idno>
<idno type="eISSN">1533-4406</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>BACKGROUND</title>
<p id="P1">Genetic mutations drive the pathogenesis of the myelodysplastic syndrome (MDS) and are closely associated with clinical phenotype. Therefore, genetic mutations may predict clinical outcomes after allogeneic hematopoietic stem-cell transplantation.</p>
</sec>
<sec id="S2"><title>METHODS</title>
<p id="P2">We performed targeted mutational analysis on samples obtained before transplantation from 1514 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research Repository between 2005 and 2014. We evaluated the association of mutations with transplantation outcomes, including overall survival, relapse, and death without relapse.</p>
</sec>
<sec id="S3"><title>RESULTS</title>
<p id="P3"><italic>TP53</italic>
mutations were present in 19% of the patients and were associated with shorter survival and a shorter time to relapse than was the absence of <italic>TP53</italic>
mutations, after adjustment for significant clinical variables (P<0.001 for both comparisons). Among patients 40 years of age or older who did not have <italic>TP53</italic>
mutations, the presence of RAS pathway mutations was associated with shorter survival than was the absence of RAS pathway mutations (P= 0.004), owing to a high risk of relapse, and the presence of <italic>JAK2</italic>
mutations was associated with shorter survival than was the absence of <italic>JAK2</italic>
mutations (P = 0.001), owing to a high risk of death without relapse. The adverse prognostic effect of <italic>TP53</italic>
mutations was similar in patients who received reduced-intensity conditioning regimens and those who received myeloablative conditioning regimens. By contrast, the adverse effect of RAS pathway mutations on the risk of relapse, as compared with the absence of RAS pathway mutations, was evident only with reduced-intensity conditioning (P<0.001). In young adults, 4% of the patients had compound heterozygous mutations in the Shwachman–Diamond syndrome–associated <italic>SBDS</italic>
gene with concurrent <italic>TP53</italic>
mutations and a poor prognosis. Mutations in the p53 regulator <italic>PPM1D</italic>
were more common among patients with therapy-related MDS than those with primary MDS (15% vs. 3%, P<0.001).</p>
</sec>
<sec id="S4"><title>CONCLUSIONS</title>
<p id="P4">Genetic profiling revealed that molecular subgroups of patients undergoing allogeneic hematopoietic stem-cell transplantation for MDS may inform prognostic stratification and the selection of conditioning regimen. (Funded by the Edward P. Evans Foundation and others.)</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list></list>
<tree><noCountry><name sortKey="Antin, J H" sort="Antin, J H" uniqKey="Antin J" first="J. H." last="Antin">J. H. Antin</name>
<name sortKey="Cutler, C" sort="Cutler, C" uniqKey="Cutler C" first="C." last="Cutler">C. Cutler</name>
<name sortKey="Ebert, B L" sort="Ebert, B L" uniqKey="Ebert B" first="B. L." last="Ebert">B. L. Ebert</name>
<name sortKey="Fleischhauer, K" sort="Fleischhauer, K" uniqKey="Fleischhauer K" first="K." last="Fleischhauer">K. Fleischhauer</name>
<name sortKey="Grauman, P V" sort="Grauman, P V" uniqKey="Grauman P" first="P. V." last="Grauman">P. V. Grauman</name>
<name sortKey="Haagenson, M D" sort="Haagenson, M D" uniqKey="Haagenson M" first="M. D." last="Haagenson">M. D. Haagenson</name>
<name sortKey="Hsu, K" sort="Hsu, K" uniqKey="Hsu K" first="K." last="Hsu">K. Hsu</name>
<name sortKey="Hu, Z H" sort="Hu, Z H" uniqKey="Hu Z" first="Z.-H." last="Hu">Z.-H. Hu</name>
<name sortKey="Lee, S J" sort="Lee, S J" uniqKey="Lee S" first="S. J." last="Lee">S. J. Lee</name>
<name sortKey="Lindsley, R C" sort="Lindsley, R C" uniqKey="Lindsley R" first="R. C." last="Lindsley">R. C. Lindsley</name>
<name sortKey="Mar, B G" sort="Mar, B G" uniqKey="Mar B" first="B. G." last="Mar">B. G. Mar</name>
<name sortKey="Neuberg, D" sort="Neuberg, D" uniqKey="Neuberg D" first="D." last="Neuberg">D. Neuberg</name>
<name sortKey="Redd, R" sort="Redd, R" uniqKey="Redd R" first="R." last="Redd">R. Redd</name>
<name sortKey="Saber, W" sort="Saber, W" uniqKey="Saber W" first="W." last="Saber">W. Saber</name>
<name sortKey="Spellman, S R" sort="Spellman, S R" uniqKey="Spellman S" first="S. R." last="Spellman">S. R. Spellman</name>
<name sortKey="Verneris, M R" sort="Verneris, M R" uniqKey="Verneris M" first="M. R." last="Verneris">M. R. Verneris</name>
<name sortKey="Wang, T" sort="Wang, T" uniqKey="Wang T" first="T." last="Wang">T. Wang</name>
</noCountry>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000264 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000264 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= LymphedemaV1 |flux= Main |étape= Exploration |type= RBID |clé= PMC:5438571 |texte= Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:28177873" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a LymphedemaV1
This area was generated with Dilib version V0.6.31. |