H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias
We created a mouse model wherein conditional expression of an Mll-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human MLL-rearranged ALL. ChIP-chip analysis d...
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| Veröffentlicht in: | Cancer cell 2008-11, Vol.14 (5), p.355-368 |
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| creator | Krivtsov, Andrei V. Feng, Zhaohui Lemieux, Madeleine E. Faber, Joerg Vempati, Sridhar Sinha, Amit U. Xia, Xiaobo Jesneck, Jonathan Bracken, Adrian P. Silverman, Lewis B. Kutok, Jeffery L. Kung, Andrew L. Armstrong, Scott A. |
| description | We created a mouse model wherein conditional expression of an Mll-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human
MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4-associated gene expression profiles in murine ALLs and in human
MLL-rearranged leukemias. Human
MLL-rearranged ALLs could be distinguished from other ALLs by their H3K79 profiles, and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4-driven gene expression. |
| doi_str_mv | 10.1016/j.ccr.2008.10.001 |
| format | Article |
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MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4-associated gene expression profiles in murine ALLs and in human
MLL-rearranged leukemias. Human
MLL-rearranged ALLs could be distinguished from other ALLs by their H3K79 profiles, and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4-driven gene expression.</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/j.ccr.2008.10.001</identifier><identifier>PMID: 18977325</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Cell Differentiation ; CELLCYCLE ; Cells, Cultured ; Chromatin Immunoprecipitation ; Female ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation, Leukemic ; Gene Rearrangement ; Histone-Lysine N-Methyltransferase ; Histones - chemistry ; Histones - genetics ; Histones - metabolism ; Homeodomain Proteins - metabolism ; Humans ; Immunophenotyping ; Integrases - metabolism ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - pathology ; Lysine - chemistry ; Lysine - genetics ; Lysine - metabolism ; Male ; Methylation ; Methyltransferases - antagonists & inhibitors ; Methyltransferases - physiology ; Mice ; Mice, Transgenic ; Myeloid-Lymphoid Leukemia Protein - physiology ; Oligonucleotide Array Sequence Analysis ; Oncogene Proteins, Fusion - physiology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Principal Component Analysis ; Protein Methyltransferases - genetics ; Protein Methyltransferases - metabolism ; RNA, Small Interfering - pharmacology ; Transcription, Genetic</subject><ispartof>Cancer cell, 2008-11, Vol.14 (5), p.355-368</ispartof><rights>2008 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-358ce342bdbb315c51bda6a798f964f8ac3e7b8411ddcdfcc94aa0de25d8a0d43</citedby><cites>FETCH-LOGICAL-c480t-358ce342bdbb315c51bda6a798f964f8ac3e7b8411ddcdfcc94aa0de25d8a0d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ccr.2008.10.001$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18977325$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krivtsov, Andrei V.</creatorcontrib><creatorcontrib>Feng, Zhaohui</creatorcontrib><creatorcontrib>Lemieux, Madeleine E.</creatorcontrib><creatorcontrib>Faber, Joerg</creatorcontrib><creatorcontrib>Vempati, Sridhar</creatorcontrib><creatorcontrib>Sinha, Amit U.</creatorcontrib><creatorcontrib>Xia, Xiaobo</creatorcontrib><creatorcontrib>Jesneck, Jonathan</creatorcontrib><creatorcontrib>Bracken, Adrian P.</creatorcontrib><creatorcontrib>Silverman, Lewis B.</creatorcontrib><creatorcontrib>Kutok, Jeffery L.</creatorcontrib><creatorcontrib>Kung, Andrew L.</creatorcontrib><creatorcontrib>Armstrong, Scott A.</creatorcontrib><title>H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>We created a mouse model wherein conditional expression of an Mll-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human
MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4-associated gene expression profiles in murine ALLs and in human
MLL-rearranged leukemias. Human
MLL-rearranged ALLs could be distinguished from other ALLs by their H3K79 profiles, and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4-driven gene expression.</description><subject>Animals</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cell Differentiation</subject><subject>CELLCYCLE</subject><subject>Cells, Cultured</subject><subject>Chromatin Immunoprecipitation</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Gene Rearrangement</subject><subject>Histone-Lysine N-Methyltransferase</subject><subject>Histones - chemistry</subject><subject>Histones - genetics</subject><subject>Histones - metabolism</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Integrases - metabolism</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Lysine - chemistry</subject><subject>Lysine - genetics</subject><subject>Lysine - metabolism</subject><subject>Male</subject><subject>Methylation</subject><subject>Methyltransferases - antagonists & inhibitors</subject><subject>Methyltransferases - physiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Myeloid-Lymphoid Leukemia Protein - physiology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncogene Proteins, Fusion - physiology</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Principal Component Analysis</subject><subject>Protein Methyltransferases - genetics</subject><subject>Protein Methyltransferases - metabolism</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Transcription, Genetic</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctOwzAQRS0E4v0BbFBW7FLsOE5sISFVLVBEKljA2nLsCbjkUewEib_HVSseG1hd23PmajwXoROCRwST7Hwx0tqNEox5uI8wJlton_CcxzTj2XY4M8rijGC-hw68XwQgI7nYRXuEizynCdtH0xm9y0U0h_7lo1a97drowXWVrcFHU6hsC9F8cCtRrYlmQ6PaaF4U8fg6jQoYXqGxyh-hnUrVHo43eoierq8eJ7O4uL-5nYyLWKcc9zFlXANNk9KUJSVMM1Ialalc8EpkacWVppCXPCXEGG0qrUWqFDaQMMODpvQQXa59l0PZgNHQ9k7Vculso9yH7JSVvyutfZHP3btMmCCCJsHgbGPgurcBfC8b6zXUtWqhG7zMRE45EexfMLhRTDkPIFmD2nXeO6i-piFYrkKSCxlCkquQVk8hg9Bz-vMb3x2bVAJwsQYgLPPdgpNeW2g1GOtA99J09g_7T1wjokQ</recordid><startdate>20081104</startdate><enddate>20081104</enddate><creator>Krivtsov, Andrei V.</creator><creator>Feng, Zhaohui</creator><creator>Lemieux, Madeleine E.</creator><creator>Faber, Joerg</creator><creator>Vempati, Sridhar</creator><creator>Sinha, Amit U.</creator><creator>Xia, Xiaobo</creator><creator>Jesneck, Jonathan</creator><creator>Bracken, Adrian P.</creator><creator>Silverman, Lewis B.</creator><creator>Kutok, Jeffery L.</creator><creator>Kung, Andrew L.</creator><creator>Armstrong, Scott A.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081104</creationdate><title>H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias</title><author>Krivtsov, Andrei V. ; Feng, Zhaohui ; Lemieux, Madeleine E. ; Faber, Joerg ; Vempati, Sridhar ; Sinha, Amit U. ; Xia, Xiaobo ; Jesneck, Jonathan ; Bracken, Adrian P. ; Silverman, Lewis B. ; Kutok, Jeffery L. ; Kung, Andrew L. ; Armstrong, Scott A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-358ce342bdbb315c51bda6a798f964f8ac3e7b8411ddcdfcc94aa0de25d8a0d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cell Differentiation</topic><topic>CELLCYCLE</topic><topic>Cells, Cultured</topic><topic>Chromatin Immunoprecipitation</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Leukemic</topic><topic>Gene Rearrangement</topic><topic>Histone-Lysine N-Methyltransferase</topic><topic>Histones - chemistry</topic><topic>Histones - genetics</topic><topic>Histones - metabolism</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Integrases - metabolism</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Lysine - chemistry</topic><topic>Lysine - genetics</topic><topic>Lysine - metabolism</topic><topic>Male</topic><topic>Methylation</topic><topic>Methyltransferases - antagonists & inhibitors</topic><topic>Methyltransferases - physiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Myeloid-Lymphoid Leukemia Protein - physiology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oncogene Proteins, Fusion - physiology</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology</topic><topic>Principal Component Analysis</topic><topic>Protein Methyltransferases - genetics</topic><topic>Protein Methyltransferases - metabolism</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krivtsov, Andrei V.</creatorcontrib><creatorcontrib>Feng, Zhaohui</creatorcontrib><creatorcontrib>Lemieux, Madeleine E.</creatorcontrib><creatorcontrib>Faber, Joerg</creatorcontrib><creatorcontrib>Vempati, Sridhar</creatorcontrib><creatorcontrib>Sinha, Amit U.</creatorcontrib><creatorcontrib>Xia, Xiaobo</creatorcontrib><creatorcontrib>Jesneck, Jonathan</creatorcontrib><creatorcontrib>Bracken, Adrian P.</creatorcontrib><creatorcontrib>Silverman, Lewis B.</creatorcontrib><creatorcontrib>Kutok, Jeffery L.</creatorcontrib><creatorcontrib>Kung, Andrew L.</creatorcontrib><creatorcontrib>Armstrong, Scott A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krivtsov, Andrei V.</au><au>Feng, Zhaohui</au><au>Lemieux, Madeleine E.</au><au>Faber, Joerg</au><au>Vempati, Sridhar</au><au>Sinha, Amit U.</au><au>Xia, Xiaobo</au><au>Jesneck, Jonathan</au><au>Bracken, Adrian P.</au><au>Silverman, Lewis B.</au><au>Kutok, Jeffery L.</au><au>Kung, Andrew L.</au><au>Armstrong, Scott A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias</atitle><jtitle>Cancer cell</jtitle><addtitle>Cancer Cell</addtitle><date>2008-11-04</date><risdate>2008</risdate><volume>14</volume><issue>5</issue><spage>355</spage><epage>368</epage><pages>355-368</pages><issn>1535-6108</issn><eissn>1878-3686</eissn><abstract>We created a mouse model wherein conditional expression of an Mll-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human
MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4-associated gene expression profiles in murine ALLs and in human
MLL-rearranged leukemias. Human
MLL-rearranged ALLs could be distinguished from other ALLs by their H3K79 profiles, and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4-driven gene expression.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18977325</pmid><doi>10.1016/j.ccr.2008.10.001</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Cell Differentiation CELLCYCLE Cells, Cultured Chromatin Immunoprecipitation Female Flow Cytometry Gene Expression Profiling Gene Expression Regulation, Leukemic Gene Rearrangement Histone-Lysine N-Methyltransferase Histones - chemistry Histones - genetics Histones - metabolism Homeodomain Proteins - metabolism Humans Immunophenotyping Integrases - metabolism Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - pathology Lysine - chemistry Lysine - genetics Lysine - metabolism Male Methylation Methyltransferases - antagonists & inhibitors Methyltransferases - physiology Mice Mice, Transgenic Myeloid-Lymphoid Leukemia Protein - physiology Oligonucleotide Array Sequence Analysis Oncogene Proteins, Fusion - physiology Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology Principal Component Analysis Protein Methyltransferases - genetics Protein Methyltransferases - metabolism RNA, Small Interfering - pharmacology Transcription, Genetic |
| title | H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias |
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