{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T05:57:43Z","timestamp":1719899863607},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T00:00:00Z","timestamp":1277942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Purpose:\u2002<\/jats:bold> Wnt signaling was demonstrated to be activated in chronic lymphocytic leukemia (CLL). It is thought to be responsible for the extended survival of CLL cells <jats:italic>in vivo<\/jats:italic>. Dickkopf1 (DKK1) is known to antagonize Wnt signaling by direct high\u2010affinity binding to the extracellular domain of WNT coreceptor lipoprotein receptor\u2010related protein 6 (LRP6). The purpose of this study was to investigate the effect of DKK1 in B\u2010CLL cells <jats:italic>in vitro<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Expression of DKK1 was estimated by Western blot and real\u2010time PCR. B cells from patients with CLL and healthy donors were incubated with recombinant DKK1. Survival was measured by flow cytometry. Primers for real\u2010time PCR were designed for extracellular domain of LRP6, responsible for DKK1 binding, and the intracellular region, essential for inhibiting GSK3 \u03b2.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Healthy and CLL cells express equivalent mRNA levels of DKK1 and LRP6. After treatment of CLL cells with recombinant DKK1 (1\u2003\u03bcg\/mL) for 3\u2003h, there was no change in the levels of phosphorylated \u03b2\u2010catenin and total \u03b2\u2010catenin. Healthy B cells proved to have significantly higher levels of extracellular, DKK1 binding domain of LRP6. We estimated that in CLL cells every 6th LRP6 receptor is lacking the extracellular domain.<\/jats:p><jats:p><jats:bold>Discussion:\u2002<\/jats:bold> For the first time we show the expression of DKK1 in CLL cells. Unlike in similar tumors, the addition of DKK1 to culture of CLL cells does not inactivate WNT pathway. The reason for this could be the absence of the binding domain of LRP6. On the other hand, a truncated LRP6 without extracellular DKK1 binding domain could lead to an uncontrollable activation of WNT signaling.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2010.01494.x","type":"journal-article","created":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T19:43:38Z","timestamp":1278445418000},"page":"309-313","source":"Crossref","is-referenced-by-count":11,"title":["Evidence for non\u2010functional Dickkopf\u20101 (DKK\u20101) signaling in chronic lymphocytic leukemia (CLL)"],"prefix":"10.1111","volume":"85","author":[{"given":"Alexandra","family":"Filipovich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh K.","family":"Gandhirajan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Gehrke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon J.","family":"Poll\u2010Wolbeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl\u2010Anton","family":"Kreuzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/11319270-000000000-00000"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428190903331082"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008294"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35077108"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.11.4677-4684.2004"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00290-1"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01117"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22318"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.04.032"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-191577"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5039"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2008.060152"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3712"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190902756594"},{"key":"e_1_2_6_16_2","first-page":"3","article-title":"Direct inhibition of GSK3 beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt\/beta\u2010catenin signaling","volume":"24","author":"Piao S","year":"2008","journal-title":"PLoS ONE"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.02.044"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-206482"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0609.2010.01494.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0609.2010.01494.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T01:25:13Z","timestamp":1697419513000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0609.2010.01494.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,10]]}},"alternative-id":["10.1111\/j.1600-0609.2010.01494.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0609.2010.01494.x","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,7]]}}}