A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia
Acute myeloid leukemia (AML) is hypothesized to be sustained by self-renewing leukemia stem cells (LSCs). Recently, gene expression signatures (GES) from functionally defined AML LSC populations were reported, and expression of a ‘core enriched’ (CE) GES, representing 44 genes activated in LCSs, con...
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| creator | Metzeler, K H Maharry, K Kohlschmidt, J Volinia, S Mrózek, K Becker, H Nicolet, D Whitman, S P Mendler, J H Schwind, S Eisfeld, A-K Wu, Y-Z Powell, B L Carter, T H Wetzler, M Kolitz, J E Baer, M R Carroll, A J Stone, R M Caligiuri, M A Marcucci, G Bloomfield, C D |
| description | Acute myeloid leukemia (AML) is hypothesized to be sustained by self-renewing leukemia stem cells (LSCs). Recently, gene expression signatures (GES) from functionally defined AML LSC populations were reported, and expression of a ‘core enriched’ (CE) GES, representing 44 genes activated in LCSs, conferred shorter survival in cytogenetically normal (CN) AML. The prognostic impact of the CE GES in the context of other molecular markers, including gene mutations and microRNA (miR) expression alterations, is unknown and its clinical utility is unclear. We studied associations of the CE GES with known molecular prognosticators, miR expression profiles, and outcomes in 364 well-characterized CN-AML patients. A high CE score (CE
high
) associated with
FLT3
-internal tandem duplication,
WT1
and
RUNX1
mutations, wild-type
CEBPA
and
TET2
, and high
ERG
,
BAALC
and
miR-155
expression. CE
high
patients had a lower complete remission (CR) rate (
P
=0.003) and shorter disease-free (DFS,
P |
| doi_str_mv | 10.1038/leu.2013.181 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3890747</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A349114078</galeid><sourcerecordid>A349114078</sourcerecordid><originalsourceid>FETCH-LOGICAL-c609t-e51e98690524a4d819f44317d349cece7dbbf873d1e62a1c82f6101b5b36f6123</originalsourceid><addsrcrecordid>eNqNkl-L1DAUxYso7rr65rMEBPHBjkmTJumLMCz-g0VB9Dlk0tuZ7KbJmKTqfDc_nCkzrrOyiPShpfeXk3vvOVX1mOAFwVS-dDAtGkzogkhypzolTPC6bVtytzrFUoqadw07qR6kdInxXOT3q5OGCt42jTitfi5RyjAiA87Vzl4BWoMHBD-2EVKywaNk117nKQLSKQVjdYaEvtu8QdYPEG2IKEzZhLH81r5HGvU2ZetNRqM1MXz6sDyW28YwWAflMNL95PJBaxvtqOMOmV0OcwfZGu3cDvkQR-2QNlMGNO7ABdujMvIVjFY_rO4N2iV4dHifVV_evP58_q6--Pj2_fnyojYcd7mGlkAneYfbhmnWS9INjFEieso6AwZEv1oNUtCeAG80MbIZOMFk1a4oL18NPate7XW302qE3oDPUTt16FkFbdXNircbtQ7fFJUdFkwUgecHgRi-TpCyGm2aV649hCkpUvphhGPJ_wst7mFBC_r0L_QyTNGXTaiGs1ZQ3uJ_UkULNx2WlP2h1tqBKs6GMoiZr1bLsiZCGBayUItbqPL0xQ4TPMzW3jzw7OjABrTLmxTclEsU0k3wxR4siUkpwnC9XYLVnHNVTFdzzlXJecGfHDtyDf8OdgHqPZBKya8hHk19m-Avb80Jxg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1440290834</pqid></control><display><type>article</type><title>A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature</source><source>EZB Electronic Journals Library</source><creator>Metzeler, K H ; Maharry, K ; Kohlschmidt, J ; Volinia, S ; Mrózek, K ; Becker, H ; Nicolet, D ; Whitman, S P ; Mendler, J H ; Schwind, S ; Eisfeld, A-K ; Wu, Y-Z ; Powell, B L ; Carter, T H ; Wetzler, M ; Kolitz, J E ; Baer, M R ; Carroll, A J ; Stone, R M ; Caligiuri, M A ; Marcucci, G ; Bloomfield, C D</creator><creatorcontrib>Metzeler, K H ; Maharry, K ; Kohlschmidt, J ; Volinia, S ; Mrózek, K ; Becker, H ; Nicolet, D ; Whitman, S P ; Mendler, J H ; Schwind, S ; Eisfeld, A-K ; Wu, Y-Z ; Powell, B L ; Carter, T H ; Wetzler, M ; Kolitz, J E ; Baer, M R ; Carroll, A J ; Stone, R M ; Caligiuri, M A ; Marcucci, G ; Bloomfield, C D</creatorcontrib><description>Acute myeloid leukemia (AML) is hypothesized to be sustained by self-renewing leukemia stem cells (LSCs). Recently, gene expression signatures (GES) from functionally defined AML LSC populations were reported, and expression of a ‘core enriched’ (CE) GES, representing 44 genes activated in LCSs, conferred shorter survival in cytogenetically normal (CN) AML. The prognostic impact of the CE GES in the context of other molecular markers, including gene mutations and microRNA (miR) expression alterations, is unknown and its clinical utility is unclear. We studied associations of the CE GES with known molecular prognosticators, miR expression profiles, and outcomes in 364 well-characterized CN-AML patients. A high CE score (CE
high
) associated with
FLT3
-internal tandem duplication,
WT1
and
RUNX1
mutations, wild-type
CEBPA
and
TET2
, and high
ERG
,
BAALC
and
miR-155
expression. CE
high
patients had a lower complete remission (CR) rate (
P
=0.003) and shorter disease-free (DFS,
P
<0.001) and overall survival (OS,
P
<0.001) than CE
low
patients. These associations persisted in multivariable analyses adjusting for other prognosticators (CR,
P
=0.02; DFS,
P
<0.001; and OS,
P
<0.001). CE
high
status was accompanied by a characteristic miR expression signature. Fifteen miRs were upregulated in both younger and older CE
high
patients, including miRs relevant for stem cell function. Our results support the clinical relevance of LSCs and improve risk stratification in AML.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2013.181</identifier><identifier>PMID: 23765227</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/191/2018 ; 631/337/384/331 ; 692/699/67/1990/283/1897 ; 692/699/67/71 ; Acute myeloid leukemia ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - genetics ; Cancer ; Cancer Research ; Clinical trials ; Critical Care Medicine ; Cytogenetic Analysis ; Female ; Gene expression ; Genetic aspects ; Health aspects ; Hematology ; Humans ; Intensive ; Internal Medicine ; Kinases ; Leukemia ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - mortality ; Leukemia, Myeloid, Acute - therapy ; Male ; Medicine ; Medicine & Public Health ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; Middle Aged ; miRNA ; Mutation ; Oligonucleotide Array Sequence Analysis ; Oncology ; original-article ; Patients ; Physiological aspects ; Prognosis ; Remission ; Remission (Medicine) ; Remission Induction ; Ribonucleic acid ; RNA ; RNA sequencing ; Runx1 protein ; Stem cells ; Stem Cells - metabolism ; Stem Cells - pathology ; Survival ; Survival Rate ; Transcriptome ; Young Adult</subject><ispartof>Leukemia, 2013-10, Vol.27 (10), p.2023-2031</ispartof><rights>Macmillan Publishers Limited 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2013</rights><rights>Macmillan Publishers Limited 2013.</rights><rights>2013 Macmillan Publishers Limited All rights reserved 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c609t-e51e98690524a4d819f44317d349cece7dbbf873d1e62a1c82f6101b5b36f6123</citedby><cites>FETCH-LOGICAL-c609t-e51e98690524a4d819f44317d349cece7dbbf873d1e62a1c82f6101b5b36f6123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2013.181$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2013.181$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23765227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Metzeler, K H</creatorcontrib><creatorcontrib>Maharry, K</creatorcontrib><creatorcontrib>Kohlschmidt, J</creatorcontrib><creatorcontrib>Volinia, S</creatorcontrib><creatorcontrib>Mrózek, K</creatorcontrib><creatorcontrib>Becker, H</creatorcontrib><creatorcontrib>Nicolet, D</creatorcontrib><creatorcontrib>Whitman, S P</creatorcontrib><creatorcontrib>Mendler, J H</creatorcontrib><creatorcontrib>Schwind, S</creatorcontrib><creatorcontrib>Eisfeld, A-K</creatorcontrib><creatorcontrib>Wu, Y-Z</creatorcontrib><creatorcontrib>Powell, B L</creatorcontrib><creatorcontrib>Carter, T H</creatorcontrib><creatorcontrib>Wetzler, M</creatorcontrib><creatorcontrib>Kolitz, J E</creatorcontrib><creatorcontrib>Baer, M R</creatorcontrib><creatorcontrib>Carroll, A J</creatorcontrib><creatorcontrib>Stone, R M</creatorcontrib><creatorcontrib>Caligiuri, M A</creatorcontrib><creatorcontrib>Marcucci, G</creatorcontrib><creatorcontrib>Bloomfield, C D</creatorcontrib><title>A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Acute myeloid leukemia (AML) is hypothesized to be sustained by self-renewing leukemia stem cells (LSCs). Recently, gene expression signatures (GES) from functionally defined AML LSC populations were reported, and expression of a ‘core enriched’ (CE) GES, representing 44 genes activated in LCSs, conferred shorter survival in cytogenetically normal (CN) AML. The prognostic impact of the CE GES in the context of other molecular markers, including gene mutations and microRNA (miR) expression alterations, is unknown and its clinical utility is unclear. We studied associations of the CE GES with known molecular prognosticators, miR expression profiles, and outcomes in 364 well-characterized CN-AML patients. A high CE score (CE
high
) associated with
FLT3
-internal tandem duplication,
WT1
and
RUNX1
mutations, wild-type
CEBPA
and
TET2
, and high
ERG
,
BAALC
and
miR-155
expression. CE
high
patients had a lower complete remission (CR) rate (
P
=0.003) and shorter disease-free (DFS,
P
<0.001) and overall survival (OS,
P
<0.001) than CE
low
patients. These associations persisted in multivariable analyses adjusting for other prognosticators (CR,
P
=0.02; DFS,
P
<0.001; and OS,
P
<0.001). CE
high
status was accompanied by a characteristic miR expression signature. Fifteen miRs were upregulated in both younger and older CE
high
patients, including miRs relevant for stem cell function. Our results support the clinical relevance of LSCs and improve risk stratification in AML.</description><subject>631/208/191/2018</subject><subject>631/337/384/331</subject><subject>692/699/67/1990/283/1897</subject><subject>692/699/67/71</subject><subject>Acute myeloid leukemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Clinical trials</subject><subject>Critical Care Medicine</subject><subject>Cytogenetic Analysis</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>Humans</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - mortality</subject><subject>Leukemia, Myeloid, Acute - therapy</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Mutation</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patients</subject><subject>Physiological aspects</subject><subject>Prognosis</subject><subject>Remission</subject><subject>Remission (Medicine)</subject><subject>Remission Induction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>Runx1 protein</subject><subject>Stem cells</subject><subject>Stem Cells - metabolism</subject><subject>Stem Cells - pathology</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Transcriptome</subject><subject>Young Adult</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkl-L1DAUxYso7rr65rMEBPHBjkmTJumLMCz-g0VB9Dlk0tuZ7KbJmKTqfDc_nCkzrrOyiPShpfeXk3vvOVX1mOAFwVS-dDAtGkzogkhypzolTPC6bVtytzrFUoqadw07qR6kdInxXOT3q5OGCt42jTitfi5RyjAiA87Vzl4BWoMHBD-2EVKywaNk117nKQLSKQVjdYaEvtu8QdYPEG2IKEzZhLH81r5HGvU2ZetNRqM1MXz6sDyW28YwWAflMNL95PJBaxvtqOMOmV0OcwfZGu3cDvkQR-2QNlMGNO7ABdujMvIVjFY_rO4N2iV4dHifVV_evP58_q6--Pj2_fnyojYcd7mGlkAneYfbhmnWS9INjFEieso6AwZEv1oNUtCeAG80MbIZOMFk1a4oL18NPate7XW302qE3oDPUTt16FkFbdXNircbtQ7fFJUdFkwUgecHgRi-TpCyGm2aV649hCkpUvphhGPJ_wst7mFBC_r0L_QyTNGXTaiGs1ZQ3uJ_UkULNx2WlP2h1tqBKs6GMoiZr1bLsiZCGBayUItbqPL0xQ4TPMzW3jzw7OjABrTLmxTclEsU0k3wxR4siUkpwnC9XYLVnHNVTFdzzlXJecGfHDtyDf8OdgHqPZBKya8hHk19m-Avb80Jxg</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Metzeler, K H</creator><creator>Maharry, K</creator><creator>Kohlschmidt, J</creator><creator>Volinia, S</creator><creator>Mrózek, K</creator><creator>Becker, H</creator><creator>Nicolet, D</creator><creator>Whitman, S P</creator><creator>Mendler, J H</creator><creator>Schwind, S</creator><creator>Eisfeld, A-K</creator><creator>Wu, Y-Z</creator><creator>Powell, B L</creator><creator>Carter, T H</creator><creator>Wetzler, M</creator><creator>Kolitz, J E</creator><creator>Baer, M R</creator><creator>Carroll, A J</creator><creator>Stone, R M</creator><creator>Caligiuri, M A</creator><creator>Marcucci, G</creator><creator>Bloomfield, C D</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20131001</creationdate><title>A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia</title><author>Metzeler, K H ; Maharry, K ; Kohlschmidt, J ; Volinia, S ; Mrózek, K ; Becker, H ; Nicolet, D ; Whitman, S P ; Mendler, J H ; Schwind, S ; Eisfeld, A-K ; Wu, Y-Z ; Powell, B L ; Carter, T H ; Wetzler, M ; Kolitz, J E ; Baer, M R ; Carroll, A J ; Stone, R M ; Caligiuri, M A ; Marcucci, G ; Bloomfield, C D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c609t-e51e98690524a4d819f44317d349cece7dbbf873d1e62a1c82f6101b5b36f6123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/208/191/2018</topic><topic>631/337/384/331</topic><topic>692/699/67/1990/283/1897</topic><topic>692/699/67/71</topic><topic>Acute myeloid leukemia</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Clinical trials</topic><topic>Critical Care Medicine</topic><topic>Cytogenetic Analysis</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Hematology</topic><topic>Humans</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - mortality</topic><topic>Leukemia, Myeloid, Acute - therapy</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Mutation</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oncology</topic><topic>original-article</topic><topic>Patients</topic><topic>Physiological aspects</topic><topic>Prognosis</topic><topic>Remission</topic><topic>Remission (Medicine)</topic><topic>Remission Induction</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>Runx1 protein</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Stem Cells - pathology</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Transcriptome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Metzeler, K H</creatorcontrib><creatorcontrib>Maharry, K</creatorcontrib><creatorcontrib>Kohlschmidt, J</creatorcontrib><creatorcontrib>Volinia, S</creatorcontrib><creatorcontrib>Mrózek, K</creatorcontrib><creatorcontrib>Becker, H</creatorcontrib><creatorcontrib>Nicolet, D</creatorcontrib><creatorcontrib>Whitman, S P</creatorcontrib><creatorcontrib>Mendler, J H</creatorcontrib><creatorcontrib>Schwind, S</creatorcontrib><creatorcontrib>Eisfeld, A-K</creatorcontrib><creatorcontrib>Wu, Y-Z</creatorcontrib><creatorcontrib>Powell, B L</creatorcontrib><creatorcontrib>Carter, T H</creatorcontrib><creatorcontrib>Wetzler, M</creatorcontrib><creatorcontrib>Kolitz, J E</creatorcontrib><creatorcontrib>Baer, M R</creatorcontrib><creatorcontrib>Carroll, A J</creatorcontrib><creatorcontrib>Stone, R M</creatorcontrib><creatorcontrib>Caligiuri, M A</creatorcontrib><creatorcontrib>Marcucci, G</creatorcontrib><creatorcontrib>Bloomfield, C D</creatorcontrib><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>Bacteriology Abstracts (Microbiology B)</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Metzeler, K H</au><au>Maharry, K</au><au>Kohlschmidt, J</au><au>Volinia, S</au><au>Mrózek, K</au><au>Becker, H</au><au>Nicolet, D</au><au>Whitman, S P</au><au>Mendler, J H</au><au>Schwind, S</au><au>Eisfeld, A-K</au><au>Wu, Y-Z</au><au>Powell, B L</au><au>Carter, T H</au><au>Wetzler, M</au><au>Kolitz, J E</au><au>Baer, M R</au><au>Carroll, A J</au><au>Stone, R M</au><au>Caligiuri, M A</au><au>Marcucci, G</au><au>Bloomfield, C D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>27</volume><issue>10</issue><spage>2023</spage><epage>2031</epage><pages>2023-2031</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Acute myeloid leukemia (AML) is hypothesized to be sustained by self-renewing leukemia stem cells (LSCs). Recently, gene expression signatures (GES) from functionally defined AML LSC populations were reported, and expression of a ‘core enriched’ (CE) GES, representing 44 genes activated in LCSs, conferred shorter survival in cytogenetically normal (CN) AML. The prognostic impact of the CE GES in the context of other molecular markers, including gene mutations and microRNA (miR) expression alterations, is unknown and its clinical utility is unclear. We studied associations of the CE GES with known molecular prognosticators, miR expression profiles, and outcomes in 364 well-characterized CN-AML patients. A high CE score (CE
high
) associated with
FLT3
-internal tandem duplication,
WT1
and
RUNX1
mutations, wild-type
CEBPA
and
TET2
, and high
ERG
,
BAALC
and
miR-155
expression. CE
high
patients had a lower complete remission (CR) rate (
P
=0.003) and shorter disease-free (DFS,
P
<0.001) and overall survival (OS,
P
<0.001) than CE
low
patients. These associations persisted in multivariable analyses adjusting for other prognosticators (CR,
P
=0.02; DFS,
P
<0.001; and OS,
P
<0.001). CE
high
status was accompanied by a characteristic miR expression signature. Fifteen miRs were upregulated in both younger and older CE
high
patients, including miRs relevant for stem cell function. Our results support the clinical relevance of LSCs and improve risk stratification in AML.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23765227</pmid><doi>10.1038/leu.2013.181</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2013-10, Vol.27 (10), p.2023-2031 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3890747 |
| source | MEDLINE; SpringerLink Journals; Nature; EZB Electronic Journals Library |
| subjects | 631/208/191/2018 631/337/384/331 692/699/67/1990/283/1897 692/699/67/71 Acute myeloid leukemia Adolescent Adult Aged Aged, 80 and over Biomarkers, Tumor - genetics Cancer Cancer Research Clinical trials Critical Care Medicine Cytogenetic Analysis Female Gene expression Genetic aspects Health aspects Hematology Humans Intensive Internal Medicine Kinases Leukemia Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - mortality Leukemia, Myeloid, Acute - therapy Male Medicine Medicine & Public Health MicroRNA MicroRNAs MicroRNAs - genetics Middle Aged miRNA Mutation Oligonucleotide Array Sequence Analysis Oncology original-article Patients Physiological aspects Prognosis Remission Remission (Medicine) Remission Induction Ribonucleic acid RNA RNA sequencing Runx1 protein Stem cells Stem Cells - metabolism Stem Cells - pathology Survival Survival Rate Transcriptome Young Adult |
| title | A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T17%3A33%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20stem%20cell-like%20gene%20expression%20signature%20associates%20with%20inferior%20outcomes%20and%20a%20distinct%20microRNA%20expression%20profile%20in%20adults%20with%20primary%20cytogenetically%20normal%20acute%20myeloid%20leukemia&rft.jtitle=Leukemia&rft.au=Metzeler,%20K%20H&rft.date=2013-10-01&rft.volume=27&rft.issue=10&rft.spage=2023&rft.epage=2031&rft.pages=2023-2031&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/leu.2013.181&rft_dat=%3Cgale_pubme%3EA349114078%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1440290834&rft_id=info:pmid/23765227&rft_galeid=A349114078&rfr_iscdi=true |