Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q)
Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progressio...
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| Veröffentlicht in: | Annals of hematology 2021-06, Vol.100 (6), p.1463-1471 |
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| creator | Hecht, Anna Meyer, Julia A. Jann, Johann-Christoph Sockel, Katja Giagounidis, Aristoteles Götze, Katharina S. Letsch, Anne Haase, Detlef Schlenk, Richard F. Haferlach, Torsten Schafhausen, Philippe Bug, Gesine Lübbert, Michael Thol, Felicitas Büsche, Guntram Schuler, Esther Nowak, Verena Obländer, Julia Fey, Stephanie Müller, Nadine Metzgeroth, Georgia Hofmann, Wolf-Karsten Germing, Ulrich Nolte, Florian Reinwald, Mark Nowak, Daniel |
| description | Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progression to acute myeloid leukemia (AML). In this study, we aimed to investigate whether global DNA methylation patterns could predict response to lenalidomide. Genome-wide DNA methylation analysis using Illumina 450k methylation arrays was performed on
n
=51 patients with MDS del5q who were uniformly treated with lenalidomide in a prospective multicenter trial of the German MDS study group. To study potential direct effects of lenalidomide on DNA methylation, 17 paired samples pre- and post-treatment were analyzed. Our results revealed no relevant effect of lenalidomide on methylation status. Furthermore, methylation patterns prior to therapy could not predict lenalidomide response. However, methylation clustering identified a group of patients with a trend towards inferior overall survival. These patients showed hypermethylation of several interesting target genes, including genes of relevant signaling pathways, potentially indicating the evaluation of novel therapeutic targets. |
| doi_str_mv | 10.1007/s00277-021-04492-1 |
| format | Article |
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=51 patients with MDS del5q who were uniformly treated with lenalidomide in a prospective multicenter trial of the German MDS study group. To study potential direct effects of lenalidomide on DNA methylation, 17 paired samples pre- and post-treatment were analyzed. Our results revealed no relevant effect of lenalidomide on methylation status. Furthermore, methylation patterns prior to therapy could not predict lenalidomide response. However, methylation clustering identified a group of patients with a trend towards inferior overall survival. These patients showed hypermethylation of several interesting target genes, including genes of relevant signaling pathways, potentially indicating the evaluation of novel therapeutic targets.</description><identifier>ISSN: 0939-5555</identifier><identifier>ISSN: 1432-0584</identifier><identifier>EISSN: 1432-0584</identifier><identifier>DOI: 10.1007/s00277-021-04492-1</identifier><identifier>PMID: 33903952</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Chromosome Deletion ; Chromosomes, Human, Pair 5 - genetics ; DNA methylation ; DNA Methylation - drug effects ; Female ; Genomes ; Hematology ; Humans ; Immunotherapy ; Lenalidomide - pharmacology ; Lenalidomide - therapeutic use ; Male ; Medical prognosis ; Medicine ; Medicine & Public Health ; Middle Aged ; Myelodysplastic syndromes ; Myelodysplastic Syndromes - drug therapy ; Myelodysplastic Syndromes - genetics ; Oncology ; Original ; Original Article ; Targeted cancer therapy ; Treatment Outcome</subject><ispartof>Annals of hematology, 2021-06, Vol.100 (6), p.1463-1471</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. 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><cites>FETCH-LOGICAL-c425t-7af9403be36d644fee07bf4bd9aed838865ca30e441fa061aa0d5dc9a915c9d73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00277-021-04492-1$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00277-021-04492-1$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33903952$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hecht, Anna</creatorcontrib><creatorcontrib>Meyer, Julia A.</creatorcontrib><creatorcontrib>Jann, Johann-Christoph</creatorcontrib><creatorcontrib>Sockel, Katja</creatorcontrib><creatorcontrib>Giagounidis, Aristoteles</creatorcontrib><creatorcontrib>Götze, Katharina S.</creatorcontrib><creatorcontrib>Letsch, Anne</creatorcontrib><creatorcontrib>Haase, Detlef</creatorcontrib><creatorcontrib>Schlenk, Richard F.</creatorcontrib><creatorcontrib>Haferlach, Torsten</creatorcontrib><creatorcontrib>Schafhausen, Philippe</creatorcontrib><creatorcontrib>Bug, Gesine</creatorcontrib><creatorcontrib>Lübbert, Michael</creatorcontrib><creatorcontrib>Thol, Felicitas</creatorcontrib><creatorcontrib>Büsche, Guntram</creatorcontrib><creatorcontrib>Schuler, Esther</creatorcontrib><creatorcontrib>Nowak, Verena</creatorcontrib><creatorcontrib>Obländer, Julia</creatorcontrib><creatorcontrib>Fey, Stephanie</creatorcontrib><creatorcontrib>Müller, Nadine</creatorcontrib><creatorcontrib>Metzgeroth, Georgia</creatorcontrib><creatorcontrib>Hofmann, Wolf-Karsten</creatorcontrib><creatorcontrib>Germing, Ulrich</creatorcontrib><creatorcontrib>Nolte, Florian</creatorcontrib><creatorcontrib>Reinwald, Mark</creatorcontrib><creatorcontrib>Nowak, Daniel</creatorcontrib><title>Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q)</title><title>Annals of hematology</title><addtitle>Ann Hematol</addtitle><addtitle>Ann Hematol</addtitle><description>Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progression to acute myeloid leukemia (AML). In this study, we aimed to investigate whether global DNA methylation patterns could predict response to lenalidomide. Genome-wide DNA methylation analysis using Illumina 450k methylation arrays was performed on
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=51 patients with MDS del5q who were uniformly treated with lenalidomide in a prospective multicenter trial of the German MDS study group. To study potential direct effects of lenalidomide on DNA methylation, 17 paired samples pre- and post-treatment were analyzed. Our results revealed no relevant effect of lenalidomide on methylation status. Furthermore, methylation patterns prior to therapy could not predict lenalidomide response. However, methylation clustering identified a group of patients with a trend towards inferior overall survival. These patients showed hypermethylation of several interesting target genes, including genes of relevant signaling pathways, potentially indicating the evaluation of novel therapeutic targets.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Chromosome Deletion</subject><subject>Chromosomes, Human, Pair 5 - genetics</subject><subject>DNA methylation</subject><subject>DNA Methylation - drug effects</subject><subject>Female</subject><subject>Genomes</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Lenalidomide - pharmacology</subject><subject>Lenalidomide - therapeutic use</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Myelodysplastic syndromes</subject><subject>Myelodysplastic Syndromes - drug therapy</subject><subject>Myelodysplastic Syndromes - genetics</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Targeted cancer therapy</subject><subject>Treatment Outcome</subject><issn>0939-5555</issn><issn>1432-0584</issn><issn>1432-0584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UUtvFSEUJkZjr9U_4MKQuKkLlOfMsDFpqlaTRje6JtzhTC8NM0yBazO_wr8st1PrYyEbOJzvceBD6Dmjrxml7ZtMKW9bQjkjVErNCXuANkwKTqjq5EO0oVpoouo6Qk9yvqKU8U7yx-hICE2FVnyDfpzDFEcgN94Bfvf5FI9QdkuwxccJ28mGJfuM5wSkVg7PMRcSoN57F8cDpySwZYSpYD_hufLqMeMbX3Z4XCBEt-Q52Fx8j_MyuVTN1q7PsdqAww4C3NqdqOtXT9GjwYYMz-72Y_Ttw_uvZx_JxZfzT2enF6SXXBXS2kFLKrYgGtdIOQDQdjvIrdMWXCe6rlG9FRSkZIOlDbOWOuV6bTVTvXatOEZvV915vx3B9XXqZIOZkx9tWky03vzdmfzOXMbvpmOs4VJUgZM7gRSv95CLGX3uIQQ7QdxnwxXrtKas0RX68h_oVdyn-ocHFFedlq1oKoqvqD7FnBMM98Mwag55mzVvU_M2t3kbVkkv_nzGPeVXwBUgVkCurekS0m_v_8j-BHWkuhQ</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Hecht, Anna</creator><creator>Meyer, Julia A.</creator><creator>Jann, Johann-Christoph</creator><creator>Sockel, Katja</creator><creator>Giagounidis, Aristoteles</creator><creator>Götze, Katharina S.</creator><creator>Letsch, Anne</creator><creator>Haase, Detlef</creator><creator>Schlenk, Richard F.</creator><creator>Haferlach, Torsten</creator><creator>Schafhausen, Philippe</creator><creator>Bug, Gesine</creator><creator>Lübbert, Michael</creator><creator>Thol, Felicitas</creator><creator>Büsche, Guntram</creator><creator>Schuler, Esther</creator><creator>Nowak, Verena</creator><creator>Obländer, Julia</creator><creator>Fey, Stephanie</creator><creator>Müller, Nadine</creator><creator>Metzgeroth, Georgia</creator><creator>Hofmann, Wolf-Karsten</creator><creator>Germing, Ulrich</creator><creator>Nolte, Florian</creator><creator>Reinwald, Mark</creator><creator>Nowak, Daniel</creator><general>Springer Berlin Heidelberg</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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210601</creationdate><title>Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q)</title><author>Hecht, Anna ; Meyer, Julia A. ; Jann, Johann-Christoph ; Sockel, Katja ; Giagounidis, Aristoteles ; Götze, Katharina S. ; Letsch, Anne ; Haase, Detlef ; Schlenk, Richard F. ; Haferlach, Torsten ; Schafhausen, Philippe ; Bug, Gesine ; Lübbert, Michael ; Thol, Felicitas ; Büsche, Guntram ; Schuler, Esther ; Nowak, Verena ; Obländer, Julia ; Fey, Stephanie ; Müller, Nadine ; Metzgeroth, Georgia ; Hofmann, Wolf-Karsten ; Germing, Ulrich ; Nolte, Florian ; Reinwald, Mark ; Nowak, Daniel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-7af9403be36d644fee07bf4bd9aed838865ca30e441fa061aa0d5dc9a915c9d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Agents - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hecht, Anna</au><au>Meyer, Julia A.</au><au>Jann, Johann-Christoph</au><au>Sockel, Katja</au><au>Giagounidis, Aristoteles</au><au>Götze, Katharina S.</au><au>Letsch, Anne</au><au>Haase, Detlef</au><au>Schlenk, Richard F.</au><au>Haferlach, Torsten</au><au>Schafhausen, Philippe</au><au>Bug, Gesine</au><au>Lübbert, Michael</au><au>Thol, Felicitas</au><au>Büsche, Guntram</au><au>Schuler, Esther</au><au>Nowak, Verena</au><au>Obländer, Julia</au><au>Fey, Stephanie</au><au>Müller, Nadine</au><au>Metzgeroth, Georgia</au><au>Hofmann, Wolf-Karsten</au><au>Germing, Ulrich</au><au>Nolte, Florian</au><au>Reinwald, Mark</au><au>Nowak, Daniel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q)</atitle><jtitle>Annals of hematology</jtitle><stitle>Ann Hematol</stitle><addtitle>Ann Hematol</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>100</volume><issue>6</issue><spage>1463</spage><epage>1471</epage><pages>1463-1471</pages><issn>0939-5555</issn><issn>1432-0584</issn><eissn>1432-0584</eissn><abstract>Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progression to acute myeloid leukemia (AML). In this study, we aimed to investigate whether global DNA methylation patterns could predict response to lenalidomide. Genome-wide DNA methylation analysis using Illumina 450k methylation arrays was performed on
n
=51 patients with MDS del5q who were uniformly treated with lenalidomide in a prospective multicenter trial of the German MDS study group. To study potential direct effects of lenalidomide on DNA methylation, 17 paired samples pre- and post-treatment were analyzed. Our results revealed no relevant effect of lenalidomide on methylation status. Furthermore, methylation patterns prior to therapy could not predict lenalidomide response. However, methylation clustering identified a group of patients with a trend towards inferior overall survival. These patients showed hypermethylation of several interesting target genes, including genes of relevant signaling pathways, potentially indicating the evaluation of novel therapeutic targets.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>33903952</pmid><doi>10.1007/s00277-021-04492-1</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Annals of hematology, 2021-06, Vol.100 (6), p.1463-1471 |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Chromosome Deletion Chromosomes, Human, Pair 5 - genetics DNA methylation DNA Methylation - drug effects Female Genomes Hematology Humans Immunotherapy Lenalidomide - pharmacology Lenalidomide - therapeutic use Male Medical prognosis Medicine Medicine & Public Health Middle Aged Myelodysplastic syndromes Myelodysplastic Syndromes - drug therapy Myelodysplastic Syndromes - genetics Oncology Original Original Article Targeted cancer therapy Treatment Outcome |
| title | Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q) |
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