PKCβ is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCβ as a therapeutic target in chronic lymphocytic leukemia

The development and the propagation of chronic lymphocytic leukemia (CLL) has been linked to signaling via the B-cell receptor (BCR). Protein kinase C β (PKCβ) is an essential signaling element of the BCR and was recently shown to be overexpressed in human CLL. We used the TCL1 transgenic mouse mode...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2009-03, Vol.113 (12), p.2791-2794
Main Authors: Holler, Claudia, Piñón, Josefina D., Denk, Ursula, Heyder, Christoph, Hofbauer, Sebastian, Greil, Richard, Egle, Alexander
Format: Article
Language:English
Subjects:
Biological and medical sciences
Hematologic and hematopoietic diseases
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c312t-f8cce2b15db4b8384e6690d34ef08dba4527ff413e1bd9ae4c1221a77cf9cd4b3
cites cdi_FETCH-LOGICAL-c312t-f8cce2b15db4b8384e6690d34ef08dba4527ff413e1bd9ae4c1221a77cf9cd4b3
container_end_page 2794
container_issue 12
container_start_page 2791
container_title Blood
container_volume 113
creator Holler, Claudia
Piñón, Josefina D.
Denk, Ursula
Heyder, Christoph
Hofbauer, Sebastian
Greil, Richard
Egle, Alexander
description The development and the propagation of chronic lymphocytic leukemia (CLL) has been linked to signaling via the B-cell receptor (BCR). Protein kinase C β (PKCβ) is an essential signaling element of the BCR and was recently shown to be overexpressed in human CLL. We used the TCL1 transgenic mouse model to directly target PKCβ in the development of murine CLL. TCL1 overexpression did restore the CD5+ B-cell population that is absent in PKCβ-deficient mice. However, PKCβ-deleted TCL1 transgenic mice did not develop a CLL disease, suggesting a role of PKCβ in the establishment of the malignant clone. Moreover, targeting of PKCβ with the specific inhibitor enzastaurin led to killing of human CLL samples in vitro. We thus propose that PKCβ may be a relevant target for the treatment of CLL.
doi_str_mv 10.1182/blood-2008-06-160713
format article
fullrecord <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1182_blood_2008_06_160713</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497120375455</els_id><sourcerecordid>S0006497120375455</sourcerecordid><originalsourceid>FETCH-LOGICAL-c312t-f8cce2b15db4b8384e6690d34ef08dba4527ff413e1bd9ae4c1221a77cf9cd4b3</originalsourceid><addsrcrecordid>eNp9kM1u3CAUhVHVSJ1O8gZdsMnSLRfjvywiVaOmjTJSs5isEYZLhsY2FjAjzWtlkcfIM9WOqy6zAXQ53zm6h5AvwL4C1Pxb23lvMs5YnbEyg5JVkH8gKyj4NGCcfSQrxqYf0VTwiXyO8Q9jIHJerMjL_d3m9Zm6SDFGHJJTHbU-0LRHavCInR_7aUy9pXof_OA07U79uPf6lOY3Hp6wd4q64Q3ZbbZAU1BDfMRZ2_tDxOk02F3Ro-qcUcn5YbZbglWkaiaDGvEwOyYVHjHNfu_lnZMzq7qIF__uNXm4-bHb_Mq2v3_ebr5vM50DT5mttUbeQmFa0dZ5LbAsG2ZygZbVplWi4JW1AnKE1jQKhQbOQVWVto02os3XRCy-OvgYA1o5BtercJLA5Ny9fOtezt1LVsql-wm7XLBRRa06OxWiXfzPcuAlVEUz6a4XHU47HB0GGbXDQaNxAXWSxrv3g_4CMvugwQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>PKCβ is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCβ as a therapeutic target in chronic lymphocytic leukemia</title><source>ScienceDirect Journals</source><creator>Holler, Claudia ; Piñón, Josefina D. ; Denk, Ursula ; Heyder, Christoph ; Hofbauer, Sebastian ; Greil, Richard ; Egle, Alexander</creator><creatorcontrib>Holler, Claudia ; Piñón, Josefina D. ; Denk, Ursula ; Heyder, Christoph ; Hofbauer, Sebastian ; Greil, Richard ; Egle, Alexander</creatorcontrib><description>The development and the propagation of chronic lymphocytic leukemia (CLL) has been linked to signaling via the B-cell receptor (BCR). Protein kinase C β (PKCβ) is an essential signaling element of the BCR and was recently shown to be overexpressed in human CLL. We used the TCL1 transgenic mouse model to directly target PKCβ in the development of murine CLL. TCL1 overexpression did restore the CD5+ B-cell population that is absent in PKCβ-deficient mice. However, PKCβ-deleted TCL1 transgenic mice did not develop a CLL disease, suggesting a role of PKCβ in the establishment of the malignant clone. Moreover, targeting of PKCβ with the specific inhibitor enzastaurin led to killing of human CLL samples in vitro. We thus propose that PKCβ may be a relevant target for the treatment of CLL.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2008-06-160713</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Biological and medical sciences ; Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences</subject><ispartof>Blood, 2009-03, Vol.113 (12), p.2791-2794</ispartof><rights>2009 American Society of Hematology</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c312t-f8cce2b15db4b8384e6690d34ef08dba4527ff413e1bd9ae4c1221a77cf9cd4b3</citedby><cites>FETCH-LOGICAL-c312t-f8cce2b15db4b8384e6690d34ef08dba4527ff413e1bd9ae4c1221a77cf9cd4b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006497120375455$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3547,27922,27923,45778</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=21261759$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Holler, Claudia</creatorcontrib><creatorcontrib>Piñón, Josefina D.</creatorcontrib><creatorcontrib>Denk, Ursula</creatorcontrib><creatorcontrib>Heyder, Christoph</creatorcontrib><creatorcontrib>Hofbauer, Sebastian</creatorcontrib><creatorcontrib>Greil, Richard</creatorcontrib><creatorcontrib>Egle, Alexander</creatorcontrib><title>PKCβ is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCβ as a therapeutic target in chronic lymphocytic leukemia</title><title>Blood</title><description>The development and the propagation of chronic lymphocytic leukemia (CLL) has been linked to signaling via the B-cell receptor (BCR). Protein kinase C β (PKCβ) is an essential signaling element of the BCR and was recently shown to be overexpressed in human CLL. We used the TCL1 transgenic mouse model to directly target PKCβ in the development of murine CLL. TCL1 overexpression did restore the CD5+ B-cell population that is absent in PKCβ-deficient mice. However, PKCβ-deleted TCL1 transgenic mice did not develop a CLL disease, suggesting a role of PKCβ in the establishment of the malignant clone. Moreover, targeting of PKCβ with the specific inhibitor enzastaurin led to killing of human CLL samples in vitro. We thus propose that PKCβ may be a relevant target for the treatment of CLL.</description><subject>Biological and medical sciences</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNp9kM1u3CAUhVHVSJ1O8gZdsMnSLRfjvywiVaOmjTJSs5isEYZLhsY2FjAjzWtlkcfIM9WOqy6zAXQ53zm6h5AvwL4C1Pxb23lvMs5YnbEyg5JVkH8gKyj4NGCcfSQrxqYf0VTwiXyO8Q9jIHJerMjL_d3m9Zm6SDFGHJJTHbU-0LRHavCInR_7aUy9pXof_OA07U79uPf6lOY3Hp6wd4q64Q3ZbbZAU1BDfMRZ2_tDxOk02F3Ro-qcUcn5YbZbglWkaiaDGvEwOyYVHjHNfu_lnZMzq7qIF__uNXm4-bHb_Mq2v3_ebr5vM50DT5mttUbeQmFa0dZ5LbAsG2ZygZbVplWi4JW1AnKE1jQKhQbOQVWVto02os3XRCy-OvgYA1o5BtercJLA5Ny9fOtezt1LVsql-wm7XLBRRa06OxWiXfzPcuAlVEUz6a4XHU47HB0GGbXDQaNxAXWSxrv3g_4CMvugwQ</recordid><startdate>20090319</startdate><enddate>20090319</enddate><creator>Holler, Claudia</creator><creator>Piñón, Josefina D.</creator><creator>Denk, Ursula</creator><creator>Heyder, Christoph</creator><creator>Hofbauer, Sebastian</creator><creator>Greil, Richard</creator><creator>Egle, Alexander</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20090319</creationdate><title>PKCβ is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCβ as a therapeutic target in chronic lymphocytic leukemia</title><author>Holler, Claudia ; Piñón, Josefina D. ; Denk, Ursula ; Heyder, Christoph ; Hofbauer, Sebastian ; Greil, Richard ; Egle, Alexander</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c312t-f8cce2b15db4b8384e6690d34ef08dba4527ff413e1bd9ae4c1221a77cf9cd4b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Biological and medical sciences</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Holler, Claudia</creatorcontrib><creatorcontrib>Piñón, Josefina D.</creatorcontrib><creatorcontrib>Denk, Ursula</creatorcontrib><creatorcontrib>Heyder, Christoph</creatorcontrib><creatorcontrib>Hofbauer, Sebastian</creatorcontrib><creatorcontrib>Greil, Richard</creatorcontrib><creatorcontrib>Egle, Alexander</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Holler, Claudia</au><au>Piñón, Josefina D.</au><au>Denk, Ursula</au><au>Heyder, Christoph</au><au>Hofbauer, Sebastian</au><au>Greil, Richard</au><au>Egle, Alexander</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PKCβ is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCβ as a therapeutic target in chronic lymphocytic leukemia</atitle><jtitle>Blood</jtitle><date>2009-03-19</date><risdate>2009</risdate><volume>113</volume><issue>12</issue><spage>2791</spage><epage>2794</epage><pages>2791-2794</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>The development and the propagation of chronic lymphocytic leukemia (CLL) has been linked to signaling via the B-cell receptor (BCR). Protein kinase C β (PKCβ) is an essential signaling element of the BCR and was recently shown to be overexpressed in human CLL. We used the TCL1 transgenic mouse model to directly target PKCβ in the development of murine CLL. TCL1 overexpression did restore the CD5+ B-cell population that is absent in PKCβ-deficient mice. However, PKCβ-deleted TCL1 transgenic mice did not develop a CLL disease, suggesting a role of PKCβ in the establishment of the malignant clone. Moreover, targeting of PKCβ with the specific inhibitor enzastaurin led to killing of human CLL samples in vitro. We thus propose that PKCβ may be a relevant target for the treatment of CLL.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><doi>10.1182/blood-2008-06-160713</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0006-4971
ispartof Blood, 2009-03, Vol.113 (12), p.2791-2794
issn 0006-4971
1528-0020
language eng
recordid cdi_crossref_primary_10_1182_blood_2008_06_160713
source ScienceDirect Journals
subjects Biological and medical sciences
Hematologic and hematopoietic diseases
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
title PKCβ is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCβ as a therapeutic target in chronic lymphocytic leukemia
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T23%3A09%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PKC%CE%B2%20is%20essential%20for%20the%20development%20of%20chronic%20lymphocytic%20leukemia%20in%20the%20TCL1%20transgenic%20mouse%20model:%20validation%20of%20PKC%CE%B2%20as%20a%20therapeutic%20target%20in%20chronic%20lymphocytic%20leukemia&rft.jtitle=Blood&rft.au=Holler,%20Claudia&rft.date=2009-03-19&rft.volume=113&rft.issue=12&rft.spage=2791&rft.epage=2794&rft.pages=2791-2794&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2008-06-160713&rft_dat=%3Celsevier_cross%3ES0006497120375455%3C/elsevier_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c312t-f8cce2b15db4b8384e6690d34ef08dba4527ff413e1bd9ae4c1221a77cf9cd4b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true