miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia
High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and pr...
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Veröffentlicht in: | Blood 2012-07, Vol.120 (2), p.249-258 |
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creator | Eisfeld, Ann-Kathrin Marcucci, Guido Maharry, Kati Schwind, Sebastian Radmacher, Michael D. Nicolet, Deedra Becker, Heiko Mrózek, Krzysztof Whitman, Susan P. Metzeler, Klaus H. Mendler, Jason H. Wu, Yue-Zhong Liyanarachchi, Sandya Patel, Ravi Baer, Maria R. Powell, Bayard L. Carter, Thomas H. Moore, Joseph O. Kolitz, Jonathan E. Wetzler, Meir Caligiuri, Michael A. Larson, Richard A. Tanner, Stephan M. de la Chapelle, Albert Bloomfield, Clara D. |
description | High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications. |
doi_str_mv | 10.1182/blood-2012-02-408492 |
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Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.</description><identifier>ISSN: 0006-4971</identifier><identifier>ISSN: 1528-0020</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2012-02-408492</identifier><identifier>PMID: 22529287</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Biological and medical sciences ; Cytogenetic Analysis ; Disease-Free Survival ; F-Box Proteins - genetics ; Female ; Gene Expression ; Hematologic and hematopoietic diseases ; Humans ; Kaplan-Meier Estimate ; Leukemia, Myeloid, Acute - genetics ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; MicroRNAs - genetics ; Middle Aged ; Myeloid Neoplasia ; Neoplasm Proteins - genetics ; Plenary Paper ; Prognosis ; RNA, Neoplasm - genetics ; Ubiquitin Thiolesterase - genetics</subject><ispartof>Blood, 2012-07, Vol.120 (2), p.249-258</ispartof><rights>2012 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><rights>2012 by The American Society of Hematology 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-22f2ee770d72d74316f147988246c133a72a970f34d5e53e16e04ab6cf89a9e3</citedby><cites>FETCH-LOGICAL-c526t-22f2ee770d72d74316f147988246c133a72a970f34d5e53e16e04ab6cf89a9e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26132920$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22529287$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eisfeld, Ann-Kathrin</creatorcontrib><creatorcontrib>Marcucci, Guido</creatorcontrib><creatorcontrib>Maharry, Kati</creatorcontrib><creatorcontrib>Schwind, Sebastian</creatorcontrib><creatorcontrib>Radmacher, Michael D.</creatorcontrib><creatorcontrib>Nicolet, Deedra</creatorcontrib><creatorcontrib>Becker, Heiko</creatorcontrib><creatorcontrib>Mrózek, Krzysztof</creatorcontrib><creatorcontrib>Whitman, Susan P.</creatorcontrib><creatorcontrib>Metzeler, Klaus H.</creatorcontrib><creatorcontrib>Mendler, Jason H.</creatorcontrib><creatorcontrib>Wu, Yue-Zhong</creatorcontrib><creatorcontrib>Liyanarachchi, Sandya</creatorcontrib><creatorcontrib>Patel, Ravi</creatorcontrib><creatorcontrib>Baer, Maria R.</creatorcontrib><creatorcontrib>Powell, Bayard L.</creatorcontrib><creatorcontrib>Carter, Thomas H.</creatorcontrib><creatorcontrib>Moore, Joseph O.</creatorcontrib><creatorcontrib>Kolitz, Jonathan E.</creatorcontrib><creatorcontrib>Wetzler, Meir</creatorcontrib><creatorcontrib>Caligiuri, Michael A.</creatorcontrib><creatorcontrib>Larson, Richard A.</creatorcontrib><creatorcontrib>Tanner, Stephan M.</creatorcontrib><creatorcontrib>de la Chapelle, Albert</creatorcontrib><creatorcontrib>Bloomfield, Clara D.</creatorcontrib><title>miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia</title><title>Blood</title><addtitle>Blood</addtitle><description>High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Cytogenetic Analysis</subject><subject>Disease-Free Survival</subject><subject>F-Box Proteins - genetics</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Myeloid Neoplasia</subject><subject>Neoplasm Proteins - genetics</subject><subject>Plenary Paper</subject><subject>Prognosis</subject><subject>RNA, Neoplasm - genetics</subject><subject>Ubiquitin Thiolesterase - genetics</subject><issn>0006-4971</issn><issn>1528-0020</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc-O0zAQhyMEYsvCGyDkCxKXgD127OSCVCr-SZWQ0N4t15lsDU5cbGdRHoJ3xqVlFy6Ii32Yb36ama-qnjL6krEWXu18CH0NlEFNoRa0FR3cq1asgbamFOj9akUplbXoFLuoHqX0hVImODQPqwuABjpo1ar6MbrPNWcNI27KGA_eLIl8d3lPXE5kH1Im1zghebNebzfETH3hejxgeabsF2KGAW0hw5xtGJGEgRxMdqV4jrFLDseE7KzxpWEKcTSeGDtnJOOCPrieeJy_4ujM4-rBYHzCJ-f_srp69_Zq86Hefnr_cbPe1rYBmWuAARCVor2CXgnO5MCE6toWhLSMc6PAdIoOXPQNNhyZRCrMTtqh7UyH_LJ6fYo9zLsRe1umjcbrQ3SjiYsOxum_K5Pb6-twoznvWiWhBLw4B8TwbcaU9eiSRe_NhGFOmklJecd5-x8oBdFxqSgrqDihNoaUIg63EzGqj871L-f66FxT0Cfnpe3Zn9vcNv2WXIDnZ8CkImGIZrIu3XGS8QLSu7NgOf2Nw6iTLSYt9i4WyboP7t-T_AQ8uMyu</recordid><startdate>20120712</startdate><enddate>20120712</enddate><creator>Eisfeld, Ann-Kathrin</creator><creator>Marcucci, Guido</creator><creator>Maharry, Kati</creator><creator>Schwind, Sebastian</creator><creator>Radmacher, Michael D.</creator><creator>Nicolet, Deedra</creator><creator>Becker, Heiko</creator><creator>Mrózek, Krzysztof</creator><creator>Whitman, Susan P.</creator><creator>Metzeler, Klaus H.</creator><creator>Mendler, Jason H.</creator><creator>Wu, Yue-Zhong</creator><creator>Liyanarachchi, Sandya</creator><creator>Patel, Ravi</creator><creator>Baer, Maria R.</creator><creator>Powell, Bayard L.</creator><creator>Carter, Thomas H.</creator><creator>Moore, Joseph O.</creator><creator>Kolitz, Jonathan E.</creator><creator>Wetzler, Meir</creator><creator>Caligiuri, Michael A.</creator><creator>Larson, Richard A.</creator><creator>Tanner, Stephan M.</creator><creator>de la Chapelle, Albert</creator><creator>Bloomfield, Clara D.</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20120712</creationdate><title>miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia</title><author>Eisfeld, Ann-Kathrin ; Marcucci, Guido ; Maharry, Kati ; Schwind, Sebastian ; Radmacher, Michael D. ; Nicolet, Deedra ; Becker, Heiko ; Mrózek, Krzysztof ; Whitman, Susan P. ; Metzeler, Klaus H. ; Mendler, Jason H. ; Wu, Yue-Zhong ; Liyanarachchi, Sandya ; Patel, Ravi ; Baer, Maria R. ; Powell, Bayard L. ; Carter, Thomas H. ; Moore, Joseph O. ; Kolitz, Jonathan E. ; Wetzler, Meir ; Caligiuri, Michael A. ; Larson, Richard A. ; Tanner, Stephan M. ; de la Chapelle, Albert ; Bloomfield, Clara D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-22f2ee770d72d74316f147988246c133a72a970f34d5e53e16e04ab6cf89a9e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Cytogenetic Analysis</topic><topic>Disease-Free Survival</topic><topic>F-Box Proteins - genetics</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemias. 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Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>22529287</pmid><doi>10.1182/blood-2012-02-408492</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Aged Aged, 80 and over Biological and medical sciences Cytogenetic Analysis Disease-Free Survival F-Box Proteins - genetics Female Gene Expression Hematologic and hematopoietic diseases Humans Kaplan-Meier Estimate Leukemia, Myeloid, Acute - genetics Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences MicroRNAs - genetics Middle Aged Myeloid Neoplasia Neoplasm Proteins - genetics Plenary Paper Prognosis RNA, Neoplasm - genetics Ubiquitin Thiolesterase - genetics |
title | miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia |
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