Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients
Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative diseases that carry intrinsically the potential for leukemic transformation. The aims of this study were (1) to detect involvement of N- and K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic...
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| Veröffentlicht in: | International journal of hematology 2002-05, Vol.75 (4), p.394-400 |
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| creator | MAVROGIANNI, Despina VINIOU, Nora MICHALI, Evi TERPOS, Evangelos MELETIS, John VAIOPOULOS, George MADZOURANI, Marina PANGALIS, Gerasimos YATAGANAS, Xenophon LOUKOPOULOS, Dimitris |
| description | Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative diseases that carry intrinsically the potential for leukemic transformation. The aims of this study were (1) to detect involvement of N- and K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic and blastic phases of PV and ET, (2) to study the occurrence of microsatellite instability (MSI) in chromosomes 5 and 7 during the chronic phase and blastic transformation of the disease, and (3) to examine the incidence of leukemia in patients treated with hydroxyurea (HU). Samples of PV and ET patients were analyzed with a polymerase chain reaction. No N- or K-ras mutations were detected. A positive score for MSI in chromosome 7 was found in 1 patient with PV during leukemic transformation. Three of 69 patients developed acute myelogenous leukemia, 2 with PV and 1 with ET. As of this report, the overall incidence of leukemic transformation is 5.7% (2/35 patients) in PV and 3.3% (1/30 patients) in ET patients treated with HU. These results indicate that (1) MSI is a genetic marker that can be detected, even in a small group of patients, at the blastic phase of the disease and (2) no increased leukemogenicity was noted in this group of patients treated with HU. |
| doi_str_mv | 10.1007/BF02982131 |
| format | Article |
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The aims of this study were (1) to detect involvement of N- and K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic and blastic phases of PV and ET, (2) to study the occurrence of microsatellite instability (MSI) in chromosomes 5 and 7 during the chronic phase and blastic transformation of the disease, and (3) to examine the incidence of leukemia in patients treated with hydroxyurea (HU). Samples of PV and ET patients were analyzed with a polymerase chain reaction. No N- or K-ras mutations were detected. A positive score for MSI in chromosome 7 was found in 1 patient with PV during leukemic transformation. Three of 69 patients developed acute myelogenous leukemia, 2 with PV and 1 with ET. As of this report, the overall incidence of leukemic transformation is 5.7% (2/35 patients) in PV and 3.3% (1/30 patients) in ET patients treated with HU. These results indicate that (1) MSI is a genetic marker that can be detected, even in a small group of patients, at the blastic phase of the disease and (2) no increased leukemogenicity was noted in this group of patients treated with HU.</description><identifier>ISSN: 0925-5710</identifier><identifier>EISSN: 1865-3774</identifier><identifier>DOI: 10.1007/BF02982131</identifier><identifier>PMID: 12041671</identifier><language>eng</language><publisher>Tokyo: Springer</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Cell Transformation, Neoplastic - chemically induced ; Cell Transformation, Neoplastic - genetics ; Chromosomes, Human, Pair 5 - genetics ; Chromosomes, Human, Pair 5 - physiology ; Chromosomes, Human, Pair 7 - genetics ; Chromosomes, Human, Pair 7 - physiology ; Drug toxicity and drugs side effects treatment ; Female ; Genes, ras - genetics ; Genes, ras - physiology ; Humans ; Hydroxyurea - adverse effects ; Hydroxyurea - therapeutic use ; Incidence ; Leukemia - chemically induced ; Leukemia - etiology ; Leukemia - genetics ; Male ; Medical sciences ; Microsatellite Repeats ; Middle Aged ; Mutation ; Pharmacology. Drug treatments ; Polycythemia Vera - complications ; Polycythemia Vera - drug therapy ; Polycythemia Vera - genetics ; Thrombocytosis - complications ; Thrombocytosis - drug therapy ; Thrombocytosis - genetics ; Toxicity: blood</subject><ispartof>International journal of hematology, 2002-05, Vol.75 (4), p.394-400</ispartof><rights>2002 INIST-CNRS</rights><rights>The Japanese Society of Hematology 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-e7c58e1a2d1c9c2db147bc0dd53013791e0a7053d829d5949ddbdf9ecd300e73</citedby><cites>FETCH-LOGICAL-c393t-e7c58e1a2d1c9c2db147bc0dd53013791e0a7053d829d5949ddbdf9ecd300e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13633107$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12041671$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MAVROGIANNI, Despina</creatorcontrib><creatorcontrib>VINIOU, Nora</creatorcontrib><creatorcontrib>MICHALI, Evi</creatorcontrib><creatorcontrib>TERPOS, Evangelos</creatorcontrib><creatorcontrib>MELETIS, John</creatorcontrib><creatorcontrib>VAIOPOULOS, George</creatorcontrib><creatorcontrib>MADZOURANI, Marina</creatorcontrib><creatorcontrib>PANGALIS, Gerasimos</creatorcontrib><creatorcontrib>YATAGANAS, Xenophon</creatorcontrib><creatorcontrib>LOUKOPOULOS, Dimitris</creatorcontrib><title>Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients</title><title>International journal of hematology</title><addtitle>Int J Hematol</addtitle><description>Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative diseases that carry intrinsically the potential for leukemic transformation. The aims of this study were (1) to detect involvement of N- and K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic and blastic phases of PV and ET, (2) to study the occurrence of microsatellite instability (MSI) in chromosomes 5 and 7 during the chronic phase and blastic transformation of the disease, and (3) to examine the incidence of leukemia in patients treated with hydroxyurea (HU). Samples of PV and ET patients were analyzed with a polymerase chain reaction. No N- or K-ras mutations were detected. A positive score for MSI in chromosome 7 was found in 1 patient with PV during leukemic transformation. Three of 69 patients developed acute myelogenous leukemia, 2 with PV and 1 with ET. As of this report, the overall incidence of leukemic transformation is 5.7% (2/35 patients) in PV and 3.3% (1/30 patients) in ET patients treated with HU. These results indicate that (1) MSI is a genetic marker that can be detected, even in a small group of patients, at the blastic phase of the disease and (2) no increased leukemogenicity was noted in this group of patients treated with HU.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Cell Transformation, Neoplastic - chemically induced</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Chromosomes, Human, Pair 5 - genetics</subject><subject>Chromosomes, Human, Pair 5 - physiology</subject><subject>Chromosomes, Human, Pair 7 - genetics</subject><subject>Chromosomes, Human, Pair 7 - physiology</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Female</subject><subject>Genes, ras - genetics</subject><subject>Genes, ras - physiology</subject><subject>Humans</subject><subject>Hydroxyurea - adverse effects</subject><subject>Hydroxyurea - therapeutic use</subject><subject>Incidence</subject><subject>Leukemia - chemically induced</subject><subject>Leukemia - etiology</subject><subject>Leukemia - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microsatellite Repeats</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Pharmacology. Drug treatments</subject><subject>Polycythemia Vera - complications</subject><subject>Polycythemia Vera - drug therapy</subject><subject>Polycythemia Vera - genetics</subject><subject>Thrombocytosis - complications</subject><subject>Thrombocytosis - drug therapy</subject><subject>Thrombocytosis - genetics</subject><subject>Toxicity: blood</subject><issn>0925-5710</issn><issn>1865-3774</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpFkcFu1DAQhi0EosvChQdAFhIXpIAdx-s1N6goIFZw6T2a2JPWbRIHT4LIK_JUONtFe7I1_vz9Gv2MvZTinRTCvP90JUq7L6WSj9hG7ne6UMZUj9lG2FIX2khxwZ4R3QkhjajMU3YhS1HJnZEb9veA8z328QaH4HgKdM9jy28Xn-KfZU4IfLrFBOPCgThwCsNNhxwyPvEw8DF2i1sy0gfgvzPIYfAcifJ7gC5_TrFv4n_kA_9RHInvRcq-fp5gCnGg46wPLkWCCbsuTJjtNEET8n1Zk9xqihR7JK6PvFnHO8vH7Mhx9Jw9aaEjfHE6t-z66vP15dfi8PPLt8uPh8Ipq6YCjdN7lFB66awrfSMr0zjhvVZCKmMlCjBCK78vrde2st43vrXovBICjdqy1w_aMcVfM9JU38U5DTmxLqVRttI5ZsvePkDrSpSwrccUekhLLUW9llafS8vwq5Nxbnr0Z_TUUgbenAAgB12bYHCBzpzaKSWFUf8AYwKiQA</recordid><startdate>20020501</startdate><enddate>20020501</enddate><creator>MAVROGIANNI, Despina</creator><creator>VINIOU, Nora</creator><creator>MICHALI, Evi</creator><creator>TERPOS, Evangelos</creator><creator>MELETIS, John</creator><creator>VAIOPOULOS, George</creator><creator>MADZOURANI, Marina</creator><creator>PANGALIS, Gerasimos</creator><creator>YATAGANAS, Xenophon</creator><creator>LOUKOPOULOS, Dimitris</creator><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20020501</creationdate><title>Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients</title><author>MAVROGIANNI, Despina ; VINIOU, Nora ; MICHALI, Evi ; TERPOS, Evangelos ; MELETIS, John ; VAIOPOULOS, George ; MADZOURANI, Marina ; PANGALIS, Gerasimos ; YATAGANAS, Xenophon ; LOUKOPOULOS, Dimitris</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-e7c58e1a2d1c9c2db147bc0dd53013791e0a7053d829d5949ddbdf9ecd300e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Cell Transformation, Neoplastic - chemically induced</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Chromosomes, Human, Pair 5 - genetics</topic><topic>Chromosomes, Human, Pair 5 - physiology</topic><topic>Chromosomes, Human, Pair 7 - genetics</topic><topic>Chromosomes, Human, Pair 7 - physiology</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Female</topic><topic>Genes, ras - genetics</topic><topic>Genes, ras - physiology</topic><topic>Humans</topic><topic>Hydroxyurea - adverse effects</topic><topic>Hydroxyurea - therapeutic use</topic><topic>Incidence</topic><topic>Leukemia - chemically induced</topic><topic>Leukemia - etiology</topic><topic>Leukemia - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microsatellite Repeats</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Pharmacology. Drug treatments</topic><topic>Polycythemia Vera - complications</topic><topic>Polycythemia Vera - drug therapy</topic><topic>Polycythemia Vera - genetics</topic><topic>Thrombocytosis - complications</topic><topic>Thrombocytosis - drug therapy</topic><topic>Thrombocytosis - genetics</topic><topic>Toxicity: blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MAVROGIANNI, Despina</creatorcontrib><creatorcontrib>VINIOU, Nora</creatorcontrib><creatorcontrib>MICHALI, Evi</creatorcontrib><creatorcontrib>TERPOS, Evangelos</creatorcontrib><creatorcontrib>MELETIS, John</creatorcontrib><creatorcontrib>VAIOPOULOS, George</creatorcontrib><creatorcontrib>MADZOURANI, Marina</creatorcontrib><creatorcontrib>PANGALIS, Gerasimos</creatorcontrib><creatorcontrib>YATAGANAS, Xenophon</creatorcontrib><creatorcontrib>LOUKOPOULOS, Dimitris</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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><jtitle>International journal of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MAVROGIANNI, Despina</au><au>VINIOU, Nora</au><au>MICHALI, Evi</au><au>TERPOS, Evangelos</au><au>MELETIS, John</au><au>VAIOPOULOS, George</au><au>MADZOURANI, Marina</au><au>PANGALIS, Gerasimos</au><au>YATAGANAS, Xenophon</au><au>LOUKOPOULOS, Dimitris</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients</atitle><jtitle>International journal of hematology</jtitle><addtitle>Int J Hematol</addtitle><date>2002-05-01</date><risdate>2002</risdate><volume>75</volume><issue>4</issue><spage>394</spage><epage>400</epage><pages>394-400</pages><issn>0925-5710</issn><eissn>1865-3774</eissn><abstract>Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative diseases that carry intrinsically the potential for leukemic transformation. The aims of this study were (1) to detect involvement of N- and K-ras mutations in codons 12 and 13 in the pathogenesis of the chronic and blastic phases of PV and ET, (2) to study the occurrence of microsatellite instability (MSI) in chromosomes 5 and 7 during the chronic phase and blastic transformation of the disease, and (3) to examine the incidence of leukemia in patients treated with hydroxyurea (HU). Samples of PV and ET patients were analyzed with a polymerase chain reaction. No N- or K-ras mutations were detected. A positive score for MSI in chromosome 7 was found in 1 patient with PV during leukemic transformation. Three of 69 patients developed acute myelogenous leukemia, 2 with PV and 1 with ET. As of this report, the overall incidence of leukemic transformation is 5.7% (2/35 patients) in PV and 3.3% (1/30 patients) in ET patients treated with HU. These results indicate that (1) MSI is a genetic marker that can be detected, even in a small group of patients, at the blastic phase of the disease and (2) no increased leukemogenicity was noted in this group of patients treated with HU.</abstract><cop>Tokyo</cop><pub>Springer</pub><pmid>12041671</pmid><doi>10.1007/BF02982131</doi><tpages>7</tpages></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Biological and medical sciences Cell Transformation, Neoplastic - chemically induced Cell Transformation, Neoplastic - genetics Chromosomes, Human, Pair 5 - genetics Chromosomes, Human, Pair 5 - physiology Chromosomes, Human, Pair 7 - genetics Chromosomes, Human, Pair 7 - physiology Drug toxicity and drugs side effects treatment Female Genes, ras - genetics Genes, ras - physiology Humans Hydroxyurea - adverse effects Hydroxyurea - therapeutic use Incidence Leukemia - chemically induced Leukemia - etiology Leukemia - genetics Male Medical sciences Microsatellite Repeats Middle Aged Mutation Pharmacology. Drug treatments Polycythemia Vera - complications Polycythemia Vera - drug therapy Polycythemia Vera - genetics Thrombocytosis - complications Thrombocytosis - drug therapy Thrombocytosis - genetics Toxicity: blood |
| title | Leukemogenic risk of hydroxyurea therapy as a single agent in polycythemia vera and essential thrombocythemia: N- and K-ras mutations and microsatellite instability in chromosomes 5 and 7 in 69 patients |
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