Cyclic nucleotide phosphodiesterase 7B mRNA: An unfavorable characteristic in chronic lymphocytic leukemia
A cost‐ and time‐efficient means to define the prognosis of patients with chronic lymphocytic leukemia (CLL) is desirable but does not yet exist. On the basis of the evidence that CLL cells have enhanced expression of the cyclic nucleotide phosphodiesterase isoform 7B (PDE7B), we hypothesized that P...
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| Veröffentlicht in: | International journal of cancer 2011-09, Vol.129 (5), p.1162-1169 |
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| creator | Zhang, Lingzhi Murray, Fiona Rassenti, Laura Z. Pu, Minya Kelly, Colleen Kanter, Joan R. Greaves, Andrew Messer, Karen Kipps, Thomas J. Insel, Paul A. |
| description | A cost‐ and time‐efficient means to define the prognosis of patients with chronic lymphocytic leukemia (CLL) is desirable but does not yet exist. On the basis of the evidence that CLL cells have enhanced expression of the cyclic nucleotide phosphodiesterase isoform 7B (PDE7B), we hypothesized that PDE7B expression might provide such information. We assessed PDE7B mRNA expression using quantitative real‐time PCR in peripheral blood mononuclear cells isolated from 85 patients and 30 normal subjects. We compared PDE7B mRNA expression with that of other disease features to determine if its expression correlates with the prognosis of patients with CLL. We found that CLL patients with PDE7B mRNA levels in the top quartile (greater than ninefold elevation relative to normal controls) have a several‐year shorter median time‐to‐treatment (TTT, 36 months) compared to that of patients whose CLL cells express lower levels of PDE7B mRNA (TTT, 77 months, p = 0.001). High PDE7B mRNA expression correlates with expression of zeta‐chain‐associated protein kinase 70 (ZAP‐70), unmutated immunoglobulin heavy chain variable (IGHV) region genes and β2 microglobulin (β2M), but use of a multivariate Cox model revealed that high PDE7B mRNA expression independently predicts a short TTT, even after adjusting for several other disease characteristics (ZAP‐70 or CD38 expression, IGHV mutation status and Rai status). High expression of PDE7B is an unfavorable characteristic in CLL. Assessment of PDE7B mRNA expression thus appears to be a clinically useful biomarker to define the prognosis of patients with CLL. |
| doi_str_mv | 10.1002/ijc.25785 |
| format | Article |
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On the basis of the evidence that CLL cells have enhanced expression of the cyclic nucleotide phosphodiesterase isoform 7B (PDE7B), we hypothesized that PDE7B expression might provide such information. We assessed PDE7B mRNA expression using quantitative real‐time PCR in peripheral blood mononuclear cells isolated from 85 patients and 30 normal subjects. We compared PDE7B mRNA expression with that of other disease features to determine if its expression correlates with the prognosis of patients with CLL. We found that CLL patients with PDE7B mRNA levels in the top quartile (greater than ninefold elevation relative to normal controls) have a several‐year shorter median time‐to‐treatment (TTT, 36 months) compared to that of patients whose CLL cells express lower levels of PDE7B mRNA (TTT, 77 months, p = 0.001). High PDE7B mRNA expression correlates with expression of zeta‐chain‐associated protein kinase 70 (ZAP‐70), unmutated immunoglobulin heavy chain variable (IGHV) region genes and β2 microglobulin (β2M), but use of a multivariate Cox model revealed that high PDE7B mRNA expression independently predicts a short TTT, even after adjusting for several other disease characteristics (ZAP‐70 or CD38 expression, IGHV mutation status and Rai status). High expression of PDE7B is an unfavorable characteristic in CLL. Assessment of PDE7B mRNA expression thus appears to be a clinically useful biomarker to define the prognosis of patients with CLL.</description><identifier>ISSN: 0020-7136</identifier><identifier>ISSN: 1097-0215</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.25785</identifier><identifier>PMID: 21120911</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>3',5'-Cyclic-nucleotide phosphodiesterase ; Adult ; Aged ; Biological and medical sciences ; biomarkers ; Case-Control Studies ; CD38 antigen ; Chronic lymphatic leukemia ; chronic lymphocytic leukemia ; cyclic nucleotide phosphodiesterase 7B ; Cyclic Nucleotide Phosphodiesterases, Type 7 - genetics ; Cyclic Nucleotide Phosphodiesterases, Type 7 - metabolism ; Disease Progression ; Female ; Follow-Up Studies ; Gene expression ; Hematologic and hematopoietic diseases ; Humans ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Heavy Chains - metabolism ; Immunoglobulin Variable Region - genetics ; Immunoglobulin Variable Region - metabolism ; Immunoglobulins ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Mutation ; Peripheral blood mononuclear cells ; Polymerase chain reaction ; Prognosis ; prognostic factor ; Protein kinase ; quantitative reverse transcriptase‐polymerase chain reaction (QPCR) ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Survival Rate ; Time Factors ; Tumors ; ZAP-70 protein ; ZAP-70 Protein-Tyrosine Kinase - genetics ; ZAP-70 Protein-Tyrosine Kinase - metabolism</subject><ispartof>International journal of cancer, 2011-09, Vol.129 (5), p.1162-1169</ispartof><rights>Copyright © 2011 UICC</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 UICC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5435-4d3254e6ab68ab156a3fa9c5d05665b8cb464c6f391d5d2340d31e565527a90c3</citedby><cites>FETCH-LOGICAL-c5435-4d3254e6ab68ab156a3fa9c5d05665b8cb464c6f391d5d2340d31e565527a90c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.25785$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.25785$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,781,785,886,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24369781$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21120911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Lingzhi</creatorcontrib><creatorcontrib>Murray, Fiona</creatorcontrib><creatorcontrib>Rassenti, Laura Z.</creatorcontrib><creatorcontrib>Pu, Minya</creatorcontrib><creatorcontrib>Kelly, Colleen</creatorcontrib><creatorcontrib>Kanter, Joan R.</creatorcontrib><creatorcontrib>Greaves, Andrew</creatorcontrib><creatorcontrib>Messer, Karen</creatorcontrib><creatorcontrib>Kipps, Thomas J.</creatorcontrib><creatorcontrib>Insel, Paul A.</creatorcontrib><title>Cyclic nucleotide phosphodiesterase 7B mRNA: An unfavorable characteristic in chronic lymphocytic leukemia</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>A cost‐ and time‐efficient means to define the prognosis of patients with chronic lymphocytic leukemia (CLL) is desirable but does not yet exist. On the basis of the evidence that CLL cells have enhanced expression of the cyclic nucleotide phosphodiesterase isoform 7B (PDE7B), we hypothesized that PDE7B expression might provide such information. We assessed PDE7B mRNA expression using quantitative real‐time PCR in peripheral blood mononuclear cells isolated from 85 patients and 30 normal subjects. We compared PDE7B mRNA expression with that of other disease features to determine if its expression correlates with the prognosis of patients with CLL. We found that CLL patients with PDE7B mRNA levels in the top quartile (greater than ninefold elevation relative to normal controls) have a several‐year shorter median time‐to‐treatment (TTT, 36 months) compared to that of patients whose CLL cells express lower levels of PDE7B mRNA (TTT, 77 months, p = 0.001). High PDE7B mRNA expression correlates with expression of zeta‐chain‐associated protein kinase 70 (ZAP‐70), unmutated immunoglobulin heavy chain variable (IGHV) region genes and β2 microglobulin (β2M), but use of a multivariate Cox model revealed that high PDE7B mRNA expression independently predicts a short TTT, even after adjusting for several other disease characteristics (ZAP‐70 or CD38 expression, IGHV mutation status and Rai status). High expression of PDE7B is an unfavorable characteristic in CLL. Assessment of PDE7B mRNA expression thus appears to be a clinically useful biomarker to define the prognosis of patients with CLL.</description><subject>3',5'-Cyclic-nucleotide phosphodiesterase</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>biomarkers</subject><subject>Case-Control Studies</subject><subject>CD38 antigen</subject><subject>Chronic lymphatic leukemia</subject><subject>chronic lymphocytic leukemia</subject><subject>cyclic nucleotide phosphodiesterase 7B</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 7 - genetics</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 7 - metabolism</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene expression</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Heavy Chains - metabolism</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Immunoglobulin Variable Region - metabolism</subject><subject>Immunoglobulins</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>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Peripheral blood mononuclear cells</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>prognostic factor</subject><subject>Protein kinase</subject><subject>quantitative reverse transcriptase‐polymerase chain reaction (QPCR)</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Survival Rate</subject><subject>Time Factors</subject><subject>Tumors</subject><subject>ZAP-70 protein</subject><subject>ZAP-70 Protein-Tyrosine Kinase - genetics</subject><subject>ZAP-70 Protein-Tyrosine Kinase - metabolism</subject><issn>0020-7136</issn><issn>1097-0215</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotvCgT-AckHAIa0n_kjCAWlZ8VFUgYTgbE0ch_Xi2Iu9aZV_j5ddChzgYNmaefSO7YeQR0DPgdLqwm70eSXqRtwhC6BtXdIKxF2yyD1a1sDkCTlNaUMpgKD8PjmpACraAizIZjVrZ3XhJ-1M2NneFNt1SHn11qSdiZhMUb8qxk8fli-KpS8mP-B1iNg5U-g1RtQZsmmXM6zPlRh8Prp5zBF63pedmb6Z0eIDcm9Al8zD435Gvrx5_Xn1rrz6-PZytbwqteBMlLxnleBGYicb7EBIZAO2WvRUSCm6Rndcci0H1kIv-opx2jMwQgpR1dhSzc7Iy0PudupG02vjdxGd2kY7YpxVQKv-7ni7Vl_DtWIA0AiaA54eA2L4PuVfUKNN2jiH3oQpqabm0EgBMpPP_ktCFtDwtmnrjD4_oDqGlKIZbi8EVO0tqmxR_bSY2cd_vuCW_KUtA0-OACaNbojotU2_Oc5kWzd77uLA3Vhn5n9PVJfvV4fRPwBXOrTF</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Zhang, Lingzhi</creator><creator>Murray, Fiona</creator><creator>Rassenti, Laura Z.</creator><creator>Pu, Minya</creator><creator>Kelly, Colleen</creator><creator>Kanter, Joan R.</creator><creator>Greaves, Andrew</creator><creator>Messer, Karen</creator><creator>Kipps, Thomas J.</creator><creator>Insel, Paul A.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</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>7TM</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110901</creationdate><title>Cyclic nucleotide phosphodiesterase 7B mRNA: An unfavorable characteristic in chronic lymphocytic leukemia</title><author>Zhang, Lingzhi ; Murray, Fiona ; Rassenti, Laura Z. ; Pu, Minya ; Kelly, Colleen ; Kanter, Joan R. ; Greaves, Andrew ; Messer, Karen ; Kipps, Thomas J. ; Insel, Paul A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5435-4d3254e6ab68ab156a3fa9c5d05665b8cb464c6f391d5d2340d31e565527a90c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>3',5'-Cyclic-nucleotide phosphodiesterase</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>biomarkers</topic><topic>Case-Control Studies</topic><topic>CD38 antigen</topic><topic>Chronic lymphatic leukemia</topic><topic>chronic lymphocytic leukemia</topic><topic>cyclic nucleotide phosphodiesterase 7B</topic><topic>Cyclic Nucleotide Phosphodiesterases, Type 7 - genetics</topic><topic>Cyclic Nucleotide Phosphodiesterases, Type 7 - metabolism</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene expression</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulin Heavy Chains - metabolism</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Immunoglobulin Variable Region - metabolism</topic><topic>Immunoglobulins</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>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Peripheral blood mononuclear cells</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>prognostic factor</topic><topic>Protein kinase</topic><topic>quantitative reverse transcriptase‐polymerase chain reaction (QPCR)</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Survival Rate</topic><topic>Time Factors</topic><topic>Tumors</topic><topic>ZAP-70 protein</topic><topic>ZAP-70 Protein-Tyrosine Kinase - genetics</topic><topic>ZAP-70 Protein-Tyrosine Kinase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Lingzhi</creatorcontrib><creatorcontrib>Murray, Fiona</creatorcontrib><creatorcontrib>Rassenti, Laura Z.</creatorcontrib><creatorcontrib>Pu, Minya</creatorcontrib><creatorcontrib>Kelly, Colleen</creatorcontrib><creatorcontrib>Kanter, Joan R.</creatorcontrib><creatorcontrib>Greaves, Andrew</creatorcontrib><creatorcontrib>Messer, Karen</creatorcontrib><creatorcontrib>Kipps, Thomas J.</creatorcontrib><creatorcontrib>Insel, Paul 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>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>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Lingzhi</au><au>Murray, Fiona</au><au>Rassenti, Laura Z.</au><au>Pu, Minya</au><au>Kelly, Colleen</au><au>Kanter, Joan R.</au><au>Greaves, Andrew</au><au>Messer, Karen</au><au>Kipps, Thomas J.</au><au>Insel, Paul A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclic nucleotide phosphodiesterase 7B mRNA: An unfavorable characteristic in chronic lymphocytic leukemia</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>129</volume><issue>5</issue><spage>1162</spage><epage>1169</epage><pages>1162-1169</pages><issn>0020-7136</issn><issn>1097-0215</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>A cost‐ and time‐efficient means to define the prognosis of patients with chronic lymphocytic leukemia (CLL) is desirable but does not yet exist. On the basis of the evidence that CLL cells have enhanced expression of the cyclic nucleotide phosphodiesterase isoform 7B (PDE7B), we hypothesized that PDE7B expression might provide such information. We assessed PDE7B mRNA expression using quantitative real‐time PCR in peripheral blood mononuclear cells isolated from 85 patients and 30 normal subjects. We compared PDE7B mRNA expression with that of other disease features to determine if its expression correlates with the prognosis of patients with CLL. We found that CLL patients with PDE7B mRNA levels in the top quartile (greater than ninefold elevation relative to normal controls) have a several‐year shorter median time‐to‐treatment (TTT, 36 months) compared to that of patients whose CLL cells express lower levels of PDE7B mRNA (TTT, 77 months, p = 0.001). High PDE7B mRNA expression correlates with expression of zeta‐chain‐associated protein kinase 70 (ZAP‐70), unmutated immunoglobulin heavy chain variable (IGHV) region genes and β2 microglobulin (β2M), but use of a multivariate Cox model revealed that high PDE7B mRNA expression independently predicts a short TTT, even after adjusting for several other disease characteristics (ZAP‐70 or CD38 expression, IGHV mutation status and Rai status). High expression of PDE7B is an unfavorable characteristic in CLL. Assessment of PDE7B mRNA expression thus appears to be a clinically useful biomarker to define the prognosis of patients with CLL.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21120911</pmid><doi>10.1002/ijc.25785</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3',5'-Cyclic-nucleotide phosphodiesterase Adult Aged Biological and medical sciences biomarkers Case-Control Studies CD38 antigen Chronic lymphatic leukemia chronic lymphocytic leukemia cyclic nucleotide phosphodiesterase 7B Cyclic Nucleotide Phosphodiesterases, Type 7 - genetics Cyclic Nucleotide Phosphodiesterases, Type 7 - metabolism Disease Progression Female Follow-Up Studies Gene expression Hematologic and hematopoietic diseases Humans Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - metabolism Immunoglobulin Variable Region - genetics Immunoglobulin Variable Region - metabolism Immunoglobulins Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - metabolism Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Mutation Peripheral blood mononuclear cells Polymerase chain reaction Prognosis prognostic factor Protein kinase quantitative reverse transcriptase‐polymerase chain reaction (QPCR) Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Survival Rate Time Factors Tumors ZAP-70 protein ZAP-70 Protein-Tyrosine Kinase - genetics ZAP-70 Protein-Tyrosine Kinase - metabolism |
| title | Cyclic nucleotide phosphodiesterase 7B mRNA: An unfavorable characteristic in chronic lymphocytic leukemia |
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