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
Hauptverfasser: Zhang, Lingzhi, Murray, Fiona, Rassenti, Laura Z., Pu, Minya, Kelly, Colleen, Kanter, Joan R., Greaves, Andrew, Messer, Karen, Kipps, Thomas J., Insel, Paul A.
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container_end_page 1169
container_issue 5
container_start_page 1162
container_title International journal of cancer
container_volume 129
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
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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. 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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$$H</linktohtml><link.rule.ids>230,315,782,786,887,1419,27931,27932,45581,45582</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;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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