Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia
To investigate the role of the cell cycle regulators p21(Waf1), p27(Kip1), retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnor...
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| Veröffentlicht in: | Leukemia 2002-06, Vol.16 (6), p.1028-1034 |
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| creator | COBO, F MARTINEZ, A MONTSERRAT, E CAMPO, E PINYOL, M HERNANDEZ, L GOMEZ, M BEA, S ESTEVE, J ROZMAN, M BOSCH, F LOPEZ-GUILLERMO, A |
| description | To investigate the role of the cell cycle regulators p21(Waf1), p27(Kip1), retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnormalities. p21(Waf1)immunohistochemical expression was negative in 12 of 15 CLL (80%), whereas it was moderate or strong in three of seven RS (43%). p21(Waf1) gene was in germline configuration in all the tumors analyzed. Four immunohistochemical patterns of p53 and p21(Waf1) expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27(Kip1) gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21(Waf1) expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL. |
| doi_str_mv | 10.1038/sj.leu.2402529 |
| format | Article |
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Four immunohistochemical patterns of p53 and p21(Waf1) expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27(Kip1) gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21(Waf1) expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2402529</identifier><identifier>PMID: 12040434</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Abnormalities ; Adult ; Aged ; Biological and medical sciences ; Cancer ; Cell Cycle ; Cell Cycle Proteins - metabolism ; Chronic lymphocytic leukemia ; Configurations ; Cyclin D1 ; Cyclin D1 - metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclins - metabolism ; Female ; Genes, p53 ; Genetic aspects ; Genetic transformation ; Hematologic and hematopoietic diseases ; Humans ; Immunoreactivity ; INK4 protein ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymphatic leukemia ; Lymphoma, Large B-Cell, Diffuse - diagnosis ; Lymphoma, Large B-Cell, Diffuse - genetics ; Lymphoma, Large B-Cell, Diffuse - metabolism ; Male ; Medical sciences ; Middle Aged ; Mutation ; p53 Protein ; Retina ; Retinoblastoma ; Retinoblastoma Protein - metabolism ; Transformations ; Tumor Suppressor Proteins - metabolism ; Tumors</subject><ispartof>Leukemia, 2002-06, Vol.16 (6), p.1028-1034</ispartof><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2002</rights><rights>Macmillan Publishers Limited 2002.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-7a02c43b42feb2ab83883d5af7d391c7e6098ffde6f9c142fdc0e38b2a54a8d73</citedby><cites>FETCH-LOGICAL-c536t-7a02c43b42feb2ab83883d5af7d391c7e6098ffde6f9c142fdc0e38b2a54a8d73</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=13688043$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12040434$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>COBO, F</creatorcontrib><creatorcontrib>MARTINEZ, A</creatorcontrib><creatorcontrib>MONTSERRAT, E</creatorcontrib><creatorcontrib>CAMPO, E</creatorcontrib><creatorcontrib>PINYOL, M</creatorcontrib><creatorcontrib>HERNANDEZ, L</creatorcontrib><creatorcontrib>GOMEZ, M</creatorcontrib><creatorcontrib>BEA, S</creatorcontrib><creatorcontrib>ESTEVE, J</creatorcontrib><creatorcontrib>ROZMAN, M</creatorcontrib><creatorcontrib>BOSCH, F</creatorcontrib><creatorcontrib>LOPEZ-GUILLERMO, A</creatorcontrib><title>Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>To investigate the role of the cell cycle regulators p21(Waf1), p27(Kip1), retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnormalities. p21(Waf1)immunohistochemical expression was negative in 12 of 15 CLL (80%), whereas it was moderate or strong in three of seven RS (43%). p21(Waf1) gene was in germline configuration in all the tumors analyzed. Four immunohistochemical patterns of p53 and p21(Waf1) expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27(Kip1) gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21(Waf1) expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL.</description><subject>Abnormalities</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cell Cycle</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Chronic lymphocytic leukemia</subject><subject>Configurations</subject><subject>Cyclin D1</subject><subject>Cyclin D1 - metabolism</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclin-Dependent Kinase Inhibitor p27</subject><subject>Cyclins - metabolism</subject><subject>Female</subject><subject>Genes, p53</subject><subject>Genetic aspects</subject><subject>Genetic transformation</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunoreactivity</subject><subject>INK4 protein</subject><subject>Leukemia</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - metabolism</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lymphatic leukemia</subject><subject>Lymphoma, Large B-Cell, Diffuse - diagnosis</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>p53 Protein</subject><subject>Retina</subject><subject>Retinoblastoma</subject><subject>Retinoblastoma Protein - metabolism</subject><subject>Transformations</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Tumors</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp90s2P1CAUAHBiNO64evVoGo3uqSPf0ONm41eyxsTomTAUtoy0jFAO899LZ5uMmuiJF_jx8XgPgOcIbhEk8m3eb4MtW0whZrh7ADaICt4yxtBDsIFSipZ3mF6AJznvIVwW-WNwgTCkkBK6AfZzCbM_BNsYG0JjjqaGyd6VoOeYGh1mm_Ts45QbPzVfvRnqxFVu5qSn7GIaT4tNdI0ZUpy8acJxPAzRHOcltuWHHb1-Ch45HbJ9to6X4Pv7d99uPra3Xz58urm-bQ0jfG6FhthQsqPY2R3WO0mkJD3TTvSkQ0ZYDjvpXG-56wyqqjfQElkpo1r2glyCq_tzDyn-LDbPavR5SUxPNpasJBIcYipolW_-KwUSAtVPrfDVX3AfS5pqFgpzygQiCKGqXv5TYciY6NhvR93pYJWfXKy_aJZ71TWGSHJOED6_7KQGW0sw5BjKqQh_wu09NCnmnKxTh-RHnY4KQbU0h8p7VSug1uaoG16sjyy70fZnvnZDBa9XoLPRwdUaG5_PjnApKyS_AAzzwV4</recordid><startdate>20020601</startdate><enddate>20020601</enddate><creator>COBO, F</creator><creator>MARTINEZ, A</creator><creator>MONTSERRAT, E</creator><creator>CAMPO, E</creator><creator>PINYOL, M</creator><creator>HERNANDEZ, L</creator><creator>GOMEZ, M</creator><creator>BEA, S</creator><creator>ESTEVE, J</creator><creator>ROZMAN, M</creator><creator>BOSCH, F</creator><creator>LOPEZ-GUILLERMO, A</creator><general>Nature Publishing</general><general>Nature Publishing Group</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>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</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>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20020601</creationdate><title>Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia</title><author>COBO, F ; MARTINEZ, A ; MONTSERRAT, E ; CAMPO, E ; PINYOL, M ; HERNANDEZ, L ; GOMEZ, M ; BEA, S ; ESTEVE, J ; ROZMAN, M ; BOSCH, F ; LOPEZ-GUILLERMO, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-7a02c43b42feb2ab83883d5af7d391c7e6098ffde6f9c142fdc0e38b2a54a8d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Abnormalities</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Cell Cycle</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Chronic lymphocytic leukemia</topic><topic>Configurations</topic><topic>Cyclin D1</topic><topic>Cyclin D1 - metabolism</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclin-Dependent Kinase Inhibitor p27</topic><topic>Cyclins - metabolism</topic><topic>Female</topic><topic>Genes, p53</topic><topic>Genetic aspects</topic><topic>Genetic transformation</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunoreactivity</topic><topic>INK4 protein</topic><topic>Leukemia</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - metabolism</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lymphatic leukemia</topic><topic>Lymphoma, Large B-Cell, Diffuse - diagnosis</topic><topic>Lymphoma, Large B-Cell, Diffuse - genetics</topic><topic>Lymphoma, Large B-Cell, Diffuse - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>p53 Protein</topic><topic>Retina</topic><topic>Retinoblastoma</topic><topic>Retinoblastoma Protein - metabolism</topic><topic>Transformations</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>COBO, F</creatorcontrib><creatorcontrib>MARTINEZ, A</creatorcontrib><creatorcontrib>MONTSERRAT, E</creatorcontrib><creatorcontrib>CAMPO, E</creatorcontrib><creatorcontrib>PINYOL, M</creatorcontrib><creatorcontrib>HERNANDEZ, L</creatorcontrib><creatorcontrib>GOMEZ, M</creatorcontrib><creatorcontrib>BEA, S</creatorcontrib><creatorcontrib>ESTEVE, J</creatorcontrib><creatorcontrib>ROZMAN, M</creatorcontrib><creatorcontrib>BOSCH, F</creatorcontrib><creatorcontrib>LOPEZ-GUILLERMO, A</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>Bacteriology Abstracts (Microbiology B)</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>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS 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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science 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 Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>COBO, F</au><au>MARTINEZ, A</au><au>MONTSERRAT, E</au><au>CAMPO, E</au><au>PINYOL, M</au><au>HERNANDEZ, L</au><au>GOMEZ, M</au><au>BEA, S</au><au>ESTEVE, J</au><au>ROZMAN, M</au><au>BOSCH, F</au><au>LOPEZ-GUILLERMO, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia</atitle><jtitle>Leukemia</jtitle><addtitle>Leukemia</addtitle><date>2002-06-01</date><risdate>2002</risdate><volume>16</volume><issue>6</issue><spage>1028</spage><epage>1034</epage><pages>1028-1034</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>To investigate the role of the cell cycle regulators p21(Waf1), p27(Kip1), retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnormalities. p21(Waf1)immunohistochemical expression was negative in 12 of 15 CLL (80%), whereas it was moderate or strong in three of seven RS (43%). p21(Waf1) gene was in germline configuration in all the tumors analyzed. Four immunohistochemical patterns of p53 and p21(Waf1) expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27(Kip1) gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21(Waf1) expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>12040434</pmid><doi>10.1038/sj.leu.2402529</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Leukemia, 2002-06, Vol.16 (6), p.1028-1034 |
| issn | 0887-6924 1476-5551 |
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| source | MEDLINE; SpringerLink Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Abnormalities Adult Aged Biological and medical sciences Cancer Cell Cycle Cell Cycle Proteins - metabolism Chronic lymphocytic leukemia Configurations Cyclin D1 Cyclin D1 - metabolism Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Cyclins - metabolism Female Genes, p53 Genetic aspects Genetic transformation Hematologic and hematopoietic diseases Humans Immunoreactivity INK4 protein Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - metabolism Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphatic leukemia Lymphoma, Large B-Cell, Diffuse - diagnosis Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - metabolism Male Medical sciences Middle Aged Mutation p53 Protein Retina Retinoblastoma Retinoblastoma Protein - metabolism Transformations Tumor Suppressor Proteins - metabolism Tumors |
| title | Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T12%3A51%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multiple%20cell%20cycle%20regulator%20alterations%20in%20Richter's%20transformation%20of%20chronic%20lymphocytic%20leukemia&rft.jtitle=Leukemia&rft.au=COBO,%20F&rft.date=2002-06-01&rft.volume=16&rft.issue=6&rft.spage=1028&rft.epage=1034&rft.pages=1028-1034&rft.issn=0887-6924&rft.eissn=1476-5551&rft.coden=LEUKED&rft_id=info:doi/10.1038/sj.leu.2402529&rft_dat=%3Cgale_proqu%3EA201866312%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=220557952&rft_id=info:pmid/12040434&rft_galeid=A201866312&rfr_iscdi=true |