Rearrangements in the second intron of the RARA gene are present in a large majority of patients with acute promyelocytic leukemia and are used as molecular marker for retinoic acid-induced leukemic cell differentiation
Chromosome 17 breakpoints in translocation t(15;17), a hallmark for acute promyelocytic leukemia (APL), have been shown to disrupt the retinoic acid receptor-alpha (RARA) gene. In this study, DNA probes around the second exon of the RARA gene showed rearrangements not previously detected. Analysis o...
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Veröffentlicht in: | Blood 1991-11, Vol.78 (10), p.2696-2701 |
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creator | SAI-JUAN CHEN YUE-JUN ZHU ZHEN-YI WANG SHU CHEN LARSEN, C.-J BERGER, R JIAN-HUA TONG SHUO DONG WEI HUANG YING CHEN WEI-MIN XIANG LEI ZHANG XIU-SONG LI GUAN-QIANG QIAN |
description | Chromosome 17 breakpoints in translocation t(15;17), a hallmark for acute promyelocytic leukemia (APL), have been shown to disrupt the retinoic acid receptor-alpha (RARA) gene. In this study, DNA probes around the second exon of the RARA gene showed rearrangements not previously detected. Analysis of 25 Chinese APL cases showed that RARA gene rearrangements were present in 23 cases (92%). The breakpoints were mapped unequivocally in 22 cases within the second intron of the gene. Therefore, the RARA gene rearrangement provides us with a specific marker of the disease. Simultaneous molecular and cytologic studies showed that the RARA gene rearrangements persisted during the first 2 to 3 weeks of all-trans retinoic acid (ATRA) therapy when differentiated granulocytes predominated in bone marrow, while these rearrangements disappeared after achieving complete remission. These data indicate that ATRA induces differentiation of APL cells. |
doi_str_mv | 10.1182/blood.V78.10.2696.2696 |
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In this study, DNA probes around the second exon of the RARA gene showed rearrangements not previously detected. Analysis of 25 Chinese APL cases showed that RARA gene rearrangements were present in 23 cases (92%). The breakpoints were mapped unequivocally in 22 cases within the second intron of the gene. Therefore, the RARA gene rearrangement provides us with a specific marker of the disease. Simultaneous molecular and cytologic studies showed that the RARA gene rearrangements persisted during the first 2 to 3 weeks of all-trans retinoic acid (ATRA) therapy when differentiated granulocytes predominated in bone marrow, while these rearrangements disappeared after achieving complete remission. These data indicate that ATRA induces differentiation of APL cells.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V78.10.2696.2696</identifier><identifier>PMID: 1668609</identifier><language>eng</language><publisher>Washington, DC: The Americain Society of Hematology</publisher><subject>Adolescent ; Adult ; Biological and medical sciences ; Bone Marrow - pathology ; Carrier Proteins - genetics ; Cell Differentiation - drug effects ; Cells, Cultured ; Child ; Chromosome Banding ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 17 ; Female ; Gene Rearrangement ; Genetic Markers ; Hematologic and hematopoietic diseases ; Humans ; Introns ; Leukemia, Promyelocytic, Acute - genetics ; Leukemia, Promyelocytic, Acute - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. 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In this study, DNA probes around the second exon of the RARA gene showed rearrangements not previously detected. Analysis of 25 Chinese APL cases showed that RARA gene rearrangements were present in 23 cases (92%). The breakpoints were mapped unequivocally in 22 cases within the second intron of the gene. Therefore, the RARA gene rearrangement provides us with a specific marker of the disease. Simultaneous molecular and cytologic studies showed that the RARA gene rearrangements persisted during the first 2 to 3 weeks of all-trans retinoic acid (ATRA) therapy when differentiated granulocytes predominated in bone marrow, while these rearrangements disappeared after achieving complete remission. 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Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Receptors, Retinoic Acid</subject><subject>Restriction Mapping</subject><subject>Translocation, Genetic</subject><subject>Tretinoin - metabolism</subject><subject>Tretinoin - pharmacology</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUctu3CAURVWjdJL2E1qxqLrzBGyD7eUoSh9SpEijtluLgcuExIYpYEXzrf2ZXHtG7YbHvefB5RDyibM15215sxtCMOvfTbvGSik7uSxvyIqLsi0YK9lbsmKMyaLuGv6OXKX0xBivq1JckksuZStZtyJ_t6BiVH4PI_icqPM0PwJNoIM3eMsxeBrsUtxuthu6Bw9URaCHCAkpM0PRQcU90FE9hejycSYcVHaL4ovLj1TpKc-UMB5hCPqYnaYDTM8wOkUVOs2KUwI8JDqGAfSEkigYnyFSGyKNkJ0PSFPamcJ5M2lEnzU01TAM1DhrIaKrQ_Pg35MLq4YEH877Nfn19e7n7ffi_uHbj9vNfaFrXudCthXSuLWiFGDK1jScVU3XycqUVtpW4LdBIxlnjTJyB52SorI1dkqxA-iqa_LlpIvz_Zkg5X50aX6Q8hCm1HPZVLytBQLlCahjSCmC7Q_R4YzHnrN-TrVfUu0x1bkyB7osSPx4dph2I5j_tFOM2P987quk1WAxUO3SP5jgNW8Er14BABSxpQ</recordid><startdate>19911115</startdate><enddate>19911115</enddate><creator>SAI-JUAN CHEN</creator><creator>YUE-JUN ZHU</creator><creator>ZHEN-YI WANG</creator><creator>SHU CHEN</creator><creator>LARSEN, C.-J</creator><creator>BERGER, R</creator><creator>JIAN-HUA TONG</creator><creator>SHUO DONG</creator><creator>WEI HUANG</creator><creator>YING CHEN</creator><creator>WEI-MIN XIANG</creator><creator>LEI ZHANG</creator><creator>XIU-SONG LI</creator><creator>GUAN-QIANG QIAN</creator><general>The Americain Society of Hematology</general><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>7T5</scope><scope>H94</scope></search><sort><creationdate>19911115</creationdate><title>Rearrangements in the second intron of the RARA gene are present in a large majority of patients with acute promyelocytic leukemia and are used as molecular marker for retinoic acid-induced leukemic cell differentiation</title><author>SAI-JUAN CHEN ; YUE-JUN ZHU ; ZHEN-YI WANG ; SHU CHEN ; LARSEN, C.-J ; BERGER, R ; JIAN-HUA TONG ; SHUO DONG ; WEI HUANG ; YING CHEN ; WEI-MIN XIANG ; LEI ZHANG ; XIU-SONG LI ; GUAN-QIANG QIAN</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-683ffe1ff525ed28d710379963d2f6f85001e760107ad6be9a653f46f825bee93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow - pathology</topic><topic>Carrier Proteins - genetics</topic><topic>Cell Differentiation - drug effects</topic><topic>Cells, Cultured</topic><topic>Child</topic><topic>Chromosome Banding</topic><topic>Chromosomes, Human, Pair 11</topic><topic>Chromosomes, Human, Pair 15</topic><topic>Chromosomes, Human, Pair 17</topic><topic>Female</topic><topic>Gene Rearrangement</topic><topic>Genetic Markers</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Introns</topic><topic>Leukemia, Promyelocytic, Acute - genetics</topic><topic>Leukemia, Promyelocytic, Acute - pathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Receptors, Retinoic Acid</topic><topic>Restriction Mapping</topic><topic>Translocation, Genetic</topic><topic>Tretinoin - metabolism</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SAI-JUAN CHEN</creatorcontrib><creatorcontrib>YUE-JUN ZHU</creatorcontrib><creatorcontrib>ZHEN-YI WANG</creatorcontrib><creatorcontrib>SHU CHEN</creatorcontrib><creatorcontrib>LARSEN, C.-J</creatorcontrib><creatorcontrib>BERGER, R</creatorcontrib><creatorcontrib>JIAN-HUA TONG</creatorcontrib><creatorcontrib>SHUO DONG</creatorcontrib><creatorcontrib>WEI HUANG</creatorcontrib><creatorcontrib>YING CHEN</creatorcontrib><creatorcontrib>WEI-MIN XIANG</creatorcontrib><creatorcontrib>LEI ZHANG</creatorcontrib><creatorcontrib>XIU-SONG LI</creatorcontrib><creatorcontrib>GUAN-QIANG QIAN</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SAI-JUAN CHEN</au><au>YUE-JUN ZHU</au><au>ZHEN-YI WANG</au><au>SHU CHEN</au><au>LARSEN, C.-J</au><au>BERGER, R</au><au>JIAN-HUA TONG</au><au>SHUO DONG</au><au>WEI HUANG</au><au>YING CHEN</au><au>WEI-MIN XIANG</au><au>LEI ZHANG</au><au>XIU-SONG LI</au><au>GUAN-QIANG QIAN</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rearrangements in the second intron of the RARA gene are present in a large majority of patients with acute promyelocytic leukemia and are used as molecular marker for retinoic acid-induced leukemic cell differentiation</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>1991-11-15</date><risdate>1991</risdate><volume>78</volume><issue>10</issue><spage>2696</spage><epage>2701</epage><pages>2696-2701</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Chromosome 17 breakpoints in translocation t(15;17), a hallmark for acute promyelocytic leukemia (APL), have been shown to disrupt the retinoic acid receptor-alpha (RARA) gene. In this study, DNA probes around the second exon of the RARA gene showed rearrangements not previously detected. Analysis of 25 Chinese APL cases showed that RARA gene rearrangements were present in 23 cases (92%). The breakpoints were mapped unequivocally in 22 cases within the second intron of the gene. Therefore, the RARA gene rearrangement provides us with a specific marker of the disease. Simultaneous molecular and cytologic studies showed that the RARA gene rearrangements persisted during the first 2 to 3 weeks of all-trans retinoic acid (ATRA) therapy when differentiated granulocytes predominated in bone marrow, while these rearrangements disappeared after achieving complete remission. These data indicate that ATRA induces differentiation of APL cells.</abstract><cop>Washington, DC</cop><pub>The Americain Society of Hematology</pub><pmid>1668609</pmid><doi>10.1182/blood.V78.10.2696.2696</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Biological and medical sciences Bone Marrow - pathology Carrier Proteins - genetics Cell Differentiation - drug effects Cells, Cultured Child Chromosome Banding Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 15 Chromosomes, Human, Pair 17 Female Gene Rearrangement Genetic Markers Hematologic and hematopoietic diseases Humans Introns Leukemia, Promyelocytic, Acute - genetics Leukemia, Promyelocytic, Acute - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Receptors, Retinoic Acid Restriction Mapping Translocation, Genetic Tretinoin - metabolism Tretinoin - pharmacology |
title | Rearrangements in the second intron of the RARA gene are present in a large majority of patients with acute promyelocytic leukemia and are used as molecular marker for retinoic acid-induced leukemic cell differentiation |
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