Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome
Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study,...
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| Veröffentlicht in: | Blood cancer journal (New York) 2018-04, Vol.8 (4), p.39-13, Article 39 |
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| creator | Hou, Hsin-An Tsai, Cheng-Hong Lin, Chien-Chin Chou, Wen-Chien Kuo, Yuan-Yeh Liu, Chieh-Yu Tseng, Mei-Hsuan Peng, Yen-Ling Liu, Ming-Chih Liu, Chia-Wen Liao, Xiu-Wen Lin, Liang-In Yao, Ming Tang, Jih-Luh Tien, Hwei-Fang |
| description | Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of
CBL, IDH2, ASXL1
,
DNMT3A
, and
TP53
were independently associated with shorter survival. Patients within each IPSS-R or 2016 WHO classification-defined risk group could be stratified into two risk subgroups based on the mutational status of these five genes; patients with these poor-risk mutations had an OS shorter than others in the same risk group, but similar to those with the next higher risk category. A scoring system incorporating age, IPSS-R and five poor-risk mutations could divide the MDS patients into four risk groups (
P
|
| doi_str_mv | 10.1038/s41408-018-0074-7 |
| format | Article |
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CBL, IDH2, ASXL1
,
DNMT3A
, and
TP53
were independently associated with shorter survival. Patients within each IPSS-R or 2016 WHO classification-defined risk group could be stratified into two risk subgroups based on the mutational status of these five genes; patients with these poor-risk mutations had an OS shorter than others in the same risk group, but similar to those with the next higher risk category. A scoring system incorporating age, IPSS-R and five poor-risk mutations could divide the MDS patients into four risk groups (
P
< 0.001 for both OS and leukemia-free survival). In conclusion, integration of gene mutations in current IPSS-R improves the prognostication of MDS patients and may help identify high-risk patients for more aggressive treatment in IPSS-R lower risk group.</description><identifier>ISSN: 2044-5385</identifier><identifier>EISSN: 2044-5385</identifier><identifier>DOI: 10.1038/s41408-018-0074-7</identifier><identifier>PMID: 29618722</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/68 ; 631/67/1990/1673 ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Female ; Fourier analysis ; Genes ; Genetic Association Studies ; Genetic Predisposition to Disease ; Hematology ; Humans ; Kaplan-Meier Estimate ; Leukemia ; Male ; Middle Aged ; Mutation ; Myelodysplastic syndromes ; Myelodysplastic Syndromes - diagnosis ; Myelodysplastic Syndromes - genetics ; Myelodysplastic Syndromes - mortality ; Oncology ; Prognosis ; Proportional Hazards Models ; Young Adult</subject><ispartof>Blood cancer journal (New York), 2018-04, Vol.8 (4), p.39-13, Article 39</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-eb9057bb901b553e51dbda8835ebc3268a994ebee0d0d6c9d40bbcce522a1b983</citedby><cites>FETCH-LOGICAL-c470t-eb9057bb901b553e51dbda8835ebc3268a994ebee0d0d6c9d40bbcce522a1b983</cites><orcidid>0000-0002-6090-9000 ; 0000-0002-4174-8766</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884776/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884776/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29618722$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hou, Hsin-An</creatorcontrib><creatorcontrib>Tsai, Cheng-Hong</creatorcontrib><creatorcontrib>Lin, Chien-Chin</creatorcontrib><creatorcontrib>Chou, Wen-Chien</creatorcontrib><creatorcontrib>Kuo, Yuan-Yeh</creatorcontrib><creatorcontrib>Liu, Chieh-Yu</creatorcontrib><creatorcontrib>Tseng, Mei-Hsuan</creatorcontrib><creatorcontrib>Peng, Yen-Ling</creatorcontrib><creatorcontrib>Liu, Ming-Chih</creatorcontrib><creatorcontrib>Liu, Chia-Wen</creatorcontrib><creatorcontrib>Liao, Xiu-Wen</creatorcontrib><creatorcontrib>Lin, Liang-In</creatorcontrib><creatorcontrib>Yao, Ming</creatorcontrib><creatorcontrib>Tang, Jih-Luh</creatorcontrib><creatorcontrib>Tien, Hwei-Fang</creatorcontrib><title>Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome</title><title>Blood cancer journal (New York)</title><addtitle>Blood Cancer Journal</addtitle><addtitle>Blood Cancer J</addtitle><description>Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of
CBL, IDH2, ASXL1
,
DNMT3A
, and
TP53
were independently associated with shorter survival. Patients within each IPSS-R or 2016 WHO classification-defined risk group could be stratified into two risk subgroups based on the mutational status of these five genes; patients with these poor-risk mutations had an OS shorter than others in the same risk group, but similar to those with the next higher risk category. A scoring system incorporating age, IPSS-R and five poor-risk mutations could divide the MDS patients into four risk groups (
P
< 0.001 for both OS and leukemia-free survival). In conclusion, integration of gene mutations in current IPSS-R improves the prognostication of MDS patients and may help identify high-risk patients for more aggressive treatment in IPSS-R lower risk group.</description><subject>631/208/68</subject><subject>631/67/1990/1673</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Female</subject><subject>Fourier analysis</subject><subject>Genes</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Hematology</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Leukemia</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Myelodysplastic syndromes</subject><subject>Myelodysplastic Syndromes - diagnosis</subject><subject>Myelodysplastic Syndromes - genetics</subject><subject>Myelodysplastic Syndromes - mortality</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Young Adult</subject><issn>2044-5385</issn><issn>2044-5385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1klGP1CAQxxuj8S7nfQBfDIkvvlSBlkJfTMzl1E0u0eT0mQCd7nK2UIFd0w_ld5Rt1_M0kQSYCb_5zwBTFM8Jfk1wJd7EmtRYlJjkiXld8kfFOcV1XbJKsMcP7LPiMsY7nAdrSEvap8UZbRsiOKXnxc-NMz5MPqhkvUO-R-M-LXZE1qHeHgBtwcHipR2gAAcboUMblyC4hVQD-hz81vmYrEG3Wc-6LbqdY4IRGeWQHafgs1Cw8RuK6Zirt2bNeJKdsgcuRfTDph0aZxh8N8dpUItmnF0X_AjPiie9GiJcnvaL4uv76y9XH8ubTx82V-9uSlNznErQLWZc55VoxipgpNOdEqJioE1FG6HatgYNgDvcNabtaqy1McAoVUS3oroo3q66016P0JlcWVCDnIIdVZilV1b-feLsTm79QTIhas6bLPDqJBD89z3EJEcbDQyDcuD3UVJMKaG8bquMvvwHvfP7_LLDQhHOKo5ZpshKmeBjDNDfF0OwPPaDXPtB5n6Qx36QPMe8eHiL-4jfv58BugJxOn4ZhD-p_6_6C6RcxxA</recordid><startdate>20180404</startdate><enddate>20180404</enddate><creator>Hou, Hsin-An</creator><creator>Tsai, Cheng-Hong</creator><creator>Lin, Chien-Chin</creator><creator>Chou, Wen-Chien</creator><creator>Kuo, Yuan-Yeh</creator><creator>Liu, Chieh-Yu</creator><creator>Tseng, Mei-Hsuan</creator><creator>Peng, Yen-Ling</creator><creator>Liu, Ming-Chih</creator><creator>Liu, Chia-Wen</creator><creator>Liao, Xiu-Wen</creator><creator>Lin, Liang-In</creator><creator>Yao, Ming</creator><creator>Tang, Jih-Luh</creator><creator>Tien, Hwei-Fang</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6090-9000</orcidid><orcidid>https://orcid.org/0000-0002-4174-8766</orcidid></search><sort><creationdate>20180404</creationdate><title>Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome</title><author>Hou, Hsin-An ; Tsai, Cheng-Hong ; Lin, Chien-Chin ; Chou, Wen-Chien ; Kuo, Yuan-Yeh ; Liu, Chieh-Yu ; Tseng, Mei-Hsuan ; Peng, Yen-Ling ; Liu, Ming-Chih ; Liu, Chia-Wen ; Liao, Xiu-Wen ; Lin, Liang-In ; Yao, Ming ; Tang, Jih-Luh ; Tien, Hwei-Fang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-eb9057bb901b553e51dbda8835ebc3268a994ebee0d0d6c9d40bbcce522a1b983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>631/208/68</topic><topic>631/67/1990/1673</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Female</topic><topic>Fourier analysis</topic><topic>Genes</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Hematology</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Leukemia</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Myelodysplastic syndromes</topic><topic>Myelodysplastic Syndromes - diagnosis</topic><topic>Myelodysplastic Syndromes - genetics</topic><topic>Myelodysplastic Syndromes - mortality</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hou, Hsin-An</creatorcontrib><creatorcontrib>Tsai, Cheng-Hong</creatorcontrib><creatorcontrib>Lin, Chien-Chin</creatorcontrib><creatorcontrib>Chou, Wen-Chien</creatorcontrib><creatorcontrib>Kuo, Yuan-Yeh</creatorcontrib><creatorcontrib>Liu, Chieh-Yu</creatorcontrib><creatorcontrib>Tseng, Mei-Hsuan</creatorcontrib><creatorcontrib>Peng, Yen-Ling</creatorcontrib><creatorcontrib>Liu, Ming-Chih</creatorcontrib><creatorcontrib>Liu, Chia-Wen</creatorcontrib><creatorcontrib>Liao, Xiu-Wen</creatorcontrib><creatorcontrib>Lin, Liang-In</creatorcontrib><creatorcontrib>Yao, Ming</creatorcontrib><creatorcontrib>Tang, Jih-Luh</creatorcontrib><creatorcontrib>Tien, Hwei-Fang</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood cancer journal (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hou, Hsin-An</au><au>Tsai, Cheng-Hong</au><au>Lin, Chien-Chin</au><au>Chou, Wen-Chien</au><au>Kuo, Yuan-Yeh</au><au>Liu, Chieh-Yu</au><au>Tseng, Mei-Hsuan</au><au>Peng, Yen-Ling</au><au>Liu, Ming-Chih</au><au>Liu, Chia-Wen</au><au>Liao, Xiu-Wen</au><au>Lin, Liang-In</au><au>Yao, Ming</au><au>Tang, Jih-Luh</au><au>Tien, Hwei-Fang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome</atitle><jtitle>Blood cancer journal (New York)</jtitle><stitle>Blood Cancer Journal</stitle><addtitle>Blood Cancer J</addtitle><date>2018-04-04</date><risdate>2018</risdate><volume>8</volume><issue>4</issue><spage>39</spage><epage>13</epage><pages>39-13</pages><artnum>39</artnum><issn>2044-5385</issn><eissn>2044-5385</eissn><abstract>Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of
CBL, IDH2, ASXL1
,
DNMT3A
, and
TP53
were independently associated with shorter survival. Patients within each IPSS-R or 2016 WHO classification-defined risk group could be stratified into two risk subgroups based on the mutational status of these five genes; patients with these poor-risk mutations had an OS shorter than others in the same risk group, but similar to those with the next higher risk category. A scoring system incorporating age, IPSS-R and five poor-risk mutations could divide the MDS patients into four risk groups (
P
< 0.001 for both OS and leukemia-free survival). In conclusion, integration of gene mutations in current IPSS-R improves the prognostication of MDS patients and may help identify high-risk patients for more aggressive treatment in IPSS-R lower risk group.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29618722</pmid><doi>10.1038/s41408-018-0074-7</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6090-9000</orcidid><orcidid>https://orcid.org/0000-0002-4174-8766</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/208/68 631/67/1990/1673 Adolescent Adult Aged Aged, 80 and over Biomarkers, Tumor Biomedical and Life Sciences Biomedicine Cancer Research Female Fourier analysis Genes Genetic Association Studies Genetic Predisposition to Disease Hematology Humans Kaplan-Meier Estimate Leukemia Male Middle Aged Mutation Myelodysplastic syndromes Myelodysplastic Syndromes - diagnosis Myelodysplastic Syndromes - genetics Myelodysplastic Syndromes - mortality Oncology Prognosis Proportional Hazards Models Young Adult |
| title | Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome |
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