{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:50:49Z","timestamp":1791355849304,"version":"4.3.1"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T00:00:00Z","timestamp":1153267200000},"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":[[2006,10]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold>  <jats:italic>Objective:<\/jats:italic>\u2002Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients. Furthermore, the use of serum TK measurement to identify subcategories of disease within those defined by IgV<jats:sub>H<\/jats:sub> mutational status, gene usage and chromosomal aberrations was investigated. <jats:italic>Methods:<\/jats:italic>\u2002Ninety\u2010one CLL patients were enrolled. Serum TK levels were measured using a radioenzyme assay. IgV<jats:sub>H<\/jats:sub> mutational status and V<jats:sub>H<\/jats:sub> gene usage were determined using BIOMED\u20102 primers and protocol. Recurring chromosomal abnormalities were detected by interphase fluorescent <jats:italic>in situ<\/jats:italic> hybridisation (FISH). Flow cytometry and reverse transcriptase polymerase chain reaction (RT\u2010PCR) determined CD38 and Zap\u201070 expression, respectively. <jats:italic>Results:<\/jats:italic>\u2002Significantly higher serum TK levels were found in IgV<jats:sub>H<\/jats:sub> unmutated, compared with IgV<jats:sub>H<\/jats:sub> mutated, patients (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001). Elevated TK levels were also found in patients with CD38 and Zap\u201070 positivity (<jats:italic>P<\/jats:italic>\u2003=\u20030.004, <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001, respectively), short lymphocyte doubling time (LDT) (<jats:italic>P<\/jats:italic>\u2003=\u20030.044) and poor or intermediate prognosis chromosomal aberrations (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001). <jats:italic>Conclusion:<\/jats:italic>\u2002A TK level of &gt;8.5\u2003U\/L best identified patients with progressive disease. Elevated TK levels could identify patients categorised, at diagnosis, into good prognosis subgroups by the various biological markers (mutated IgV<jats:sub>H<\/jats:sub>, good prognosis chromosomal aberrations, Zap\u201070<jats:sup>\u2212<\/jats:sup> and CD38<jats:sup>\u2212<\/jats:sup>) who subsequently showed disease progression. Additionally, patients with V<jats:sub>H<\/jats:sub>3\u201021 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2006.00707.x","type":"journal-article","created":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T15:13:05Z","timestamp":1153408385000},"page":"309-317","source":"Crossref","is-referenced-by-count":32,"title":["Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression"],"prefix":"10.1111","volume":"77","author":[{"given":"Christine","family":"Matthews","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Catherwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. C. M.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Kettle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary B.","family":"Drake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Gilmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Denis","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,19]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199510193331606"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1840"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1848"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050350"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012283432602"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.4.1410.h81602001410_1410_1416"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.3.1023"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.4.1177.h81602001177_1177_1184"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3306"},{"key":"e_1_2_6_11_2","first-page":"348:1764","article-title":"ZAP\u201070 expression as a surrogate for immunoglobulin\u2010variable\u2010region mutations in chronic lymphocytic leukemia","author":"Crespo M","year":"2003","journal-title":"N Engl J Med"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15260-9"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040857"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402537"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.3.814"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401194"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.7.2455"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.6.1892"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.11.1639"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-3344"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1718"},{"key":"e_1_2_6_22_2","first-page":"465","article-title":"Patients with chronic lymphocytic leukemia with mutated VH genes presenting with Binet stage B or C form a subgroup with a poor outcome","volume":"90","author":"Tobin G","year":"2005","journal-title":"Haematologica"},{"key":"e_1_2_6_23_2","first-page":"606a","article-title":"The serum \u03b22 microglobulin (\u03b22M) level is more powerful than stage in predicting response and survival in chronic lymphocytic leukaemia (CLL)","volume":"86","author":"Keating MJ","year":"1998","journal-title":"Blood"},{"key":"e_1_2_6_24_2","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1182\/blood.V88.11.4259.4259","article-title":"Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia","volume":"88","author":"Sarfati M","year":"1996","journal-title":"Blood"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01715117"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.1993.8.189"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(92)90020-Z"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.22.11941"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V58.5.926.926"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1981.tb07251.x"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1983.78"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910330103"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402780"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1985.tb02820.x"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428199609054782"},{"key":"e_1_2_6_36_2","first-page":"1732","article-title":"Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia","volume":"93","author":"Hallek M","year":"1999","journal-title":"Blood"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403202"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1080\/10428190410001710812"},{"key":"e_1_2_6_39_2","first-page":"41","article-title":"Immunophenotyping in the differential diagnosis of mantle cell lymphoma\/leukaemia","volume":"42","author":"Alexander HD","year":"2001","journal-title":"Leuk Lymphoma"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2005.00619.x"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011138825593"},{"key":"e_1_2_6_42_2","first-page":"S55","article-title":"Prognostic significance of trisomy 12 in CLL","volume":"46","author":"Gardiner AC","year":"2005","journal-title":"Leuk Lymphoma"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.568"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/365349a0"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.21.12261"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0867"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3485"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1080\/1042819031000147018"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1385\/MO:22:3:217"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-04-1289"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2606"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2227"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-10-4073"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0609.2006.00707.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0609.2006.00707.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:22:58Z","timestamp":1696990978000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0609.2006.00707.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,7,19]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2006,10]]}},"alternative-id":["10.1111\/j.1600-0609.2006.00707.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0609.2006.00707.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":[[2006,7,19]]}}}