Acute Leukemias of Different Lineages Have Similar MLL Gene Fusions Encoding Related Chimeric Proteins Resulting from Chromosomal Translocation
The MLL gene, on human chromosome 11q23, undergoes chromosomal translocation in acute leukemias, resulting in gene fusion with AF4 (chromosome 4) and ENL (chromosome 19). We report here translocation of MLL with nine different chromosomes and two paracentric chromosome 11 deletions in early B cell,...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1993-09, Vol.90 (18), p.8538-8542 |
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| creator | Corral, J. Forster, A. Thompson, S. Lampert, F. Kaneko, Y. Slater, R. Kroes, W. G. van der Schoot, C. E. W.-D. Ludwig Karpas, A. Pocock, C. Cotter, F. Rabbitts, T. H. |
| description | The MLL gene, on human chromosome 11q23, undergoes chromosomal translocation in acute leukemias, resulting in gene fusion with AF4 (chromosome 4) and ENL (chromosome 19). We report here translocation of MLL with nine different chromosomes and two paracentric chromosome 11 deletions in early B cell, B- or T-cell lineage, or nonlymphocytic acute leukemias. The mRNA translocation junction from 22 t(4;11) patients, including six adult leukemias, and nine t(11;19) tumors reveals a remarkable conservation of breakpoints within MLL, AF4, or ENL genes, irrespective of tumor phenotype. Typically, the breakpoints are upstream of the zinc-finger region of MLL, and deletion of this region can accompany translocation, supporting the der(11) chromosome as the important component in leukemogenesis. Partial sequence of a fusion between MLL and the AFX1 gene from chromosome X shows the latter to be rich in Ser/Pro codons, like the ENL mRNA. These data suggest that the heterogeneous 11q23 abnormalities might cause attachment of Ser/Pro-rich segments to the NH2terminus of MLL, lacking the zinc-finger region, and that translocations occur in early hematopoietic cells, before commitment to distinct lineages. |
| doi_str_mv | 10.1073/pnas.90.18.8538 |
| format | Article |
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G. ; van der Schoot, C. E. ; W.-D. Ludwig ; Karpas, A. ; Pocock, C. ; Cotter, F. ; Rabbitts, T. H.</creator><creatorcontrib>Corral, J. ; Forster, A. ; Thompson, S. ; Lampert, F. ; Kaneko, Y. ; Slater, R. ; Kroes, W. G. ; van der Schoot, C. E. ; W.-D. Ludwig ; Karpas, A. ; Pocock, C. ; Cotter, F. ; Rabbitts, T. H.</creatorcontrib><description>The MLL gene, on human chromosome 11q23, undergoes chromosomal translocation in acute leukemias, resulting in gene fusion with AF4 (chromosome 4) and ENL (chromosome 19). We report here translocation of MLL with nine different chromosomes and two paracentric chromosome 11 deletions in early B cell, B- or T-cell lineage, or nonlymphocytic acute leukemias. The mRNA translocation junction from 22 t(4;11) patients, including six adult leukemias, and nine t(11;19) tumors reveals a remarkable conservation of breakpoints within MLL, AF4, or ENL genes, irrespective of tumor phenotype. Typically, the breakpoints are upstream of the zinc-finger region of MLL, and deletion of this region can accompany translocation, supporting the der(11) chromosome as the important component in leukemogenesis. Partial sequence of a fusion between MLL and the AFX1 gene from chromosome X shows the latter to be rich in Ser/Pro codons, like the ENL mRNA. These data suggest that the heterogeneous 11q23 abnormalities might cause attachment of Ser/Pro-rich segments to the NH2terminus of MLL, lacking the zinc-finger region, and that translocations occur in early hematopoietic cells, before commitment to distinct lineages.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.90.18.8538</identifier><identifier>PMID: 8378328</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>550400 - Genetics ; Acute Disease ; acute leukemia ; Amino Acid Sequence ; Base Sequence ; BASIC BIOLOGICAL SCIENCES ; Biological and medical sciences ; CHROMOSOMAL ABERRATIONS ; CHROMOSOME BREAKAGE ; Chromosome translocation ; CHROMOSOMES ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 19 ; Chromosomes, Human, Pair 4 ; Cloning, Molecular ; Codon - genetics ; Complementary DNA ; DISEASES ; DNA probes ; DNA, Neoplasm - genetics ; DNA, Neoplasm - metabolism ; DNA-Binding Proteins - genetics ; Exons ; fusion gene ; GENE MUTATIONS ; Gene Rearrangement ; GENES ; Genetic engineering ; Hematologic and hematopoietic diseases ; HETEROCHROMOSOMES ; Histone-Lysine N-Methyltransferase ; HUMAN CHROMOSOME 19 ; HUMAN CHROMOSOMES ; HUMAN X CHROMOSOME ; Humans ; IMMUNE SYSTEM DISEASES ; LEUKEMIA ; Leukemia - genetics ; Leukemia - metabolism ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; man ; Medical research ; Medical sciences ; Messenger RNA ; MLL gene ; Molecular Sequence Data ; MUTATIONS ; Myeloid-Lymphoid Leukemia Protein ; NEOPLASMS ; Oligodeoxyribonucleotides ; ORGANIC COMPOUNDS ; Phenotypes ; Polymerase Chain Reaction - methods ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; PROTEINS ; Proto-Oncogenes ; Recombinant Fusion Proteins - biosynthesis ; Restriction Mapping ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Transcription Factors ; Transcription, Genetic ; TRANSLOCATION ; Translocation, Genetic ; Tumor Cells, Cultured ; Tumors ; X CHROMOSOME ; Zinc Fingers - genetics</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1993-09, Vol.90 (18), p.8538-8542</ispartof><rights>Copyright 1993 The National Academy of Sciences of the United States of America</rights><rights>1994 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Sep 15, 1993</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c642t-b57241010dfd5ee7af7232348688ccac7df8c8b9bff15435ae8d625b2f2fa58e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/90/18.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2362885$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2362885$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3767215$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8378328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/5105020$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Corral, J.</creatorcontrib><creatorcontrib>Forster, A.</creatorcontrib><creatorcontrib>Thompson, S.</creatorcontrib><creatorcontrib>Lampert, F.</creatorcontrib><creatorcontrib>Kaneko, Y.</creatorcontrib><creatorcontrib>Slater, R.</creatorcontrib><creatorcontrib>Kroes, W. G.</creatorcontrib><creatorcontrib>van der Schoot, C. E.</creatorcontrib><creatorcontrib>W.-D. Ludwig</creatorcontrib><creatorcontrib>Karpas, A.</creatorcontrib><creatorcontrib>Pocock, C.</creatorcontrib><creatorcontrib>Cotter, F.</creatorcontrib><creatorcontrib>Rabbitts, T. H.</creatorcontrib><title>Acute Leukemias of Different Lineages Have Similar MLL Gene Fusions Encoding Related Chimeric Proteins Resulting from Chromosomal Translocation</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The MLL gene, on human chromosome 11q23, undergoes chromosomal translocation in acute leukemias, resulting in gene fusion with AF4 (chromosome 4) and ENL (chromosome 19). We report here translocation of MLL with nine different chromosomes and two paracentric chromosome 11 deletions in early B cell, B- or T-cell lineage, or nonlymphocytic acute leukemias. The mRNA translocation junction from 22 t(4;11) patients, including six adult leukemias, and nine t(11;19) tumors reveals a remarkable conservation of breakpoints within MLL, AF4, or ENL genes, irrespective of tumor phenotype. Typically, the breakpoints are upstream of the zinc-finger region of MLL, and deletion of this region can accompany translocation, supporting the der(11) chromosome as the important component in leukemogenesis. Partial sequence of a fusion between MLL and the AFX1 gene from chromosome X shows the latter to be rich in Ser/Pro codons, like the ENL mRNA. These data suggest that the heterogeneous 11q23 abnormalities might cause attachment of Ser/Pro-rich segments to the NH2terminus of MLL, lacking the zinc-finger region, and that translocations occur in early hematopoietic cells, before commitment to distinct lineages.</description><subject>550400 - Genetics</subject><subject>Acute Disease</subject><subject>acute leukemia</subject><subject>Amino Acid Sequence</subject><subject>Base Sequence</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Biological and medical sciences</subject><subject>CHROMOSOMAL ABERRATIONS</subject><subject>CHROMOSOME BREAKAGE</subject><subject>Chromosome translocation</subject><subject>CHROMOSOMES</subject><subject>Chromosomes, Human, Pair 11</subject><subject>Chromosomes, Human, Pair 19</subject><subject>Chromosomes, Human, Pair 4</subject><subject>Cloning, Molecular</subject><subject>Codon - genetics</subject><subject>Complementary DNA</subject><subject>DISEASES</subject><subject>DNA probes</subject><subject>DNA, Neoplasm - genetics</subject><subject>DNA, Neoplasm - metabolism</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Exons</subject><subject>fusion gene</subject><subject>GENE MUTATIONS</subject><subject>Gene Rearrangement</subject><subject>GENES</subject><subject>Genetic engineering</subject><subject>Hematologic and hematopoietic diseases</subject><subject>HETEROCHROMOSOMES</subject><subject>Histone-Lysine N-Methyltransferase</subject><subject>HUMAN CHROMOSOME 19</subject><subject>HUMAN CHROMOSOMES</subject><subject>HUMAN X CHROMOSOME</subject><subject>Humans</subject><subject>IMMUNE SYSTEM DISEASES</subject><subject>LEUKEMIA</subject><subject>Leukemia - genetics</subject><subject>Leukemia - metabolism</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>man</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Messenger RNA</subject><subject>MLL gene</subject><subject>Molecular Sequence Data</subject><subject>MUTATIONS</subject><subject>Myeloid-Lymphoid Leukemia Protein</subject><subject>NEOPLASMS</subject><subject>Oligodeoxyribonucleotides</subject><subject>ORGANIC COMPOUNDS</subject><subject>Phenotypes</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>PROTEINS</subject><subject>Proto-Oncogenes</subject><subject>Recombinant Fusion Proteins - biosynthesis</subject><subject>Restriction Mapping</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Transcription Factors</subject><subject>Transcription, Genetic</subject><subject>TRANSLOCATION</subject><subject>Translocation, Genetic</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>X CHROMOSOME</subject><subject>Zinc Fingers - genetics</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2P0zAQhiMEWpaFMxdAFkJwatd24sSRuKzKfiAFgZblbLnOuHVx7GI7K_gV_GUctZTlAhdbo_eZeTUfRfGU4DnBTXm6dTLO2xzwOWclv1ccE9ySWV21-H5xjDFtZryi1cPiUYwbjHHLOD4qjnjZ8JLy4-LnmRoToA7GrzAYGZHX6J3RGgK4hDrjQK4goit5C-izGYyVAX3oOnQJDtDFGI13EZ075XvjVugarEzQo8XaDBCMQp-CT2Aycg1xtGlidPBDBvLrox-kRTdBumi9kikXe1w80NJGeLL_T4ovF-c3i6tZ9_Hy_eKsm6m6omm2ZA2tCCa41z0DaKRuaEnLitecKyVV02uu-LJdak1YVTIJvK8pW1JNtWQcypPi7a7udlwO0KvcbZBWbIMZZPghvDTib8WZtVj5W1E1ZUtz-stduo_JiKhMArVW3jlQSTCCGaY4Q6_3HsF_GyEmMZiowFrpwI9RNKxlFanq_4KkzqaM37E9gBs_BpcHJSgmlOetswyd7iAVfIwB9KErgsV0NGI6GtHmgIvpaHLG87vDOPD7K8n6q70uo5JW54UpEw9Y2dQNJZPxmz021f-t_vERerQ2wfeUyRf_JDPwbAdsYvLhQNCypjwDvwCvgO49</recordid><startdate>19930915</startdate><enddate>19930915</enddate><creator>Corral, J.</creator><creator>Forster, A.</creator><creator>Thompson, S.</creator><creator>Lampert, F.</creator><creator>Kaneko, Y.</creator><creator>Slater, R.</creator><creator>Kroes, W. 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G. ; van der Schoot, C. E. ; W.-D. Ludwig ; Karpas, A. ; Pocock, C. ; Cotter, F. ; Rabbitts, T. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>man</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Messenger RNA</topic><topic>MLL gene</topic><topic>Molecular Sequence Data</topic><topic>MUTATIONS</topic><topic>Myeloid-Lymphoid Leukemia Protein</topic><topic>NEOPLASMS</topic><topic>Oligodeoxyribonucleotides</topic><topic>ORGANIC COMPOUNDS</topic><topic>Phenotypes</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>PROTEINS</topic><topic>Proto-Oncogenes</topic><topic>Recombinant Fusion Proteins - biosynthesis</topic><topic>Restriction Mapping</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Transcription Factors</topic><topic>Transcription, Genetic</topic><topic>TRANSLOCATION</topic><topic>Translocation, Genetic</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>X CHROMOSOME</topic><topic>Zinc Fingers - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Corral, J.</creatorcontrib><creatorcontrib>Forster, A.</creatorcontrib><creatorcontrib>Thompson, S.</creatorcontrib><creatorcontrib>Lampert, F.</creatorcontrib><creatorcontrib>Kaneko, Y.</creatorcontrib><creatorcontrib>Slater, R.</creatorcontrib><creatorcontrib>Kroes, W. G.</creatorcontrib><creatorcontrib>van der Schoot, C. E.</creatorcontrib><creatorcontrib>W.-D. Ludwig</creatorcontrib><creatorcontrib>Karpas, A.</creatorcontrib><creatorcontrib>Pocock, C.</creatorcontrib><creatorcontrib>Cotter, F.</creatorcontrib><creatorcontrib>Rabbitts, T. H.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Human Genome Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Corral, J.</au><au>Forster, A.</au><au>Thompson, S.</au><au>Lampert, F.</au><au>Kaneko, Y.</au><au>Slater, R.</au><au>Kroes, W. G.</au><au>van der Schoot, C. E.</au><au>W.-D. Ludwig</au><au>Karpas, A.</au><au>Pocock, C.</au><au>Cotter, F.</au><au>Rabbitts, T. H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute Leukemias of Different Lineages Have Similar MLL Gene Fusions Encoding Related Chimeric Proteins Resulting from Chromosomal Translocation</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1993-09-15</date><risdate>1993</risdate><volume>90</volume><issue>18</issue><spage>8538</spage><epage>8542</epage><pages>8538-8542</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>The MLL gene, on human chromosome 11q23, undergoes chromosomal translocation in acute leukemias, resulting in gene fusion with AF4 (chromosome 4) and ENL (chromosome 19). We report here translocation of MLL with nine different chromosomes and two paracentric chromosome 11 deletions in early B cell, B- or T-cell lineage, or nonlymphocytic acute leukemias. The mRNA translocation junction from 22 t(4;11) patients, including six adult leukemias, and nine t(11;19) tumors reveals a remarkable conservation of breakpoints within MLL, AF4, or ENL genes, irrespective of tumor phenotype. Typically, the breakpoints are upstream of the zinc-finger region of MLL, and deletion of this region can accompany translocation, supporting the der(11) chromosome as the important component in leukemogenesis. Partial sequence of a fusion between MLL and the AFX1 gene from chromosome X shows the latter to be rich in Ser/Pro codons, like the ENL mRNA. These data suggest that the heterogeneous 11q23 abnormalities might cause attachment of Ser/Pro-rich segments to the NH2terminus of MLL, lacking the zinc-finger region, and that translocations occur in early hematopoietic cells, before commitment to distinct lineages.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>8378328</pmid><doi>10.1073/pnas.90.18.8538</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1993-09, Vol.90 (18), p.8538-8542 |
| issn | 0027-8424 1091-6490 |
| language | eng |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 550400 - Genetics Acute Disease acute leukemia Amino Acid Sequence Base Sequence BASIC BIOLOGICAL SCIENCES Biological and medical sciences CHROMOSOMAL ABERRATIONS CHROMOSOME BREAKAGE Chromosome translocation CHROMOSOMES Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 19 Chromosomes, Human, Pair 4 Cloning, Molecular Codon - genetics Complementary DNA DISEASES DNA probes DNA, Neoplasm - genetics DNA, Neoplasm - metabolism DNA-Binding Proteins - genetics Exons fusion gene GENE MUTATIONS Gene Rearrangement GENES Genetic engineering Hematologic and hematopoietic diseases HETEROCHROMOSOMES Histone-Lysine N-Methyltransferase HUMAN CHROMOSOME 19 HUMAN CHROMOSOMES HUMAN X CHROMOSOME Humans IMMUNE SYSTEM DISEASES LEUKEMIA Leukemia - genetics Leukemia - metabolism Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis man Medical research Medical sciences Messenger RNA MLL gene Molecular Sequence Data MUTATIONS Myeloid-Lymphoid Leukemia Protein NEOPLASMS Oligodeoxyribonucleotides ORGANIC COMPOUNDS Phenotypes Polymerase Chain Reaction - methods Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics PROTEINS Proto-Oncogenes Recombinant Fusion Proteins - biosynthesis Restriction Mapping RNA, Messenger - genetics RNA, Messenger - metabolism Transcription Factors Transcription, Genetic TRANSLOCATION Translocation, Genetic Tumor Cells, Cultured Tumors X CHROMOSOME Zinc Fingers - genetics |
| title | Acute Leukemias of Different Lineages Have Similar MLL Gene Fusions Encoding Related Chimeric Proteins Resulting from Chromosomal Translocation |
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