{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T16:45:12Z","timestamp":1700671512227},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,10,26]],"date-time":"2011-10-26T00:00:00Z","timestamp":1319587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Part B Clinical"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction:<\/jats:title><jats:p>Expression of ZAP\u201070 by chronic lymphocytic leukemia (CLL) is associated with more aggressive disease and can help differentiate CLL using mutated immunoglobulin heavy chain variable genes (VH) from cases expressing unmutated VH genes. However, flow cytometric detection of ZAP\u201070 in CLL shows considerable variability and may be of questionable significance because most laboratories cannot correlate their results to clinical outcome or VH mutational data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Seventy cases of CLL were evaluated for ZAP\u201070 using a previously optimized staining procedure and two different methods to eliminate nonspecific background staining. One method, not previously reported, used isotypic control antibodies, where the concentrations were adjusted\/optimized so that normal B\u2010cells stained negatively for ZAP\u201070. The other used ZAP\u201070 stained peripheral blood B\u2010cells from normal donors. The percentages of ZAP\u201070 stained CLL cells above the two thresholds were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Concentrations of isotypic control antibodies had to be increased from manufacture's recommendations to insure normal B\u2010cells were ZAP\u201070 negative. ZAP\u201070 levels among the CLL cases formed a bimodal distribution using the optimized isotypic control threshold, with 30 having low values (0\u201332% positive) and 40 high values (60\u201399% positive). In contrast, a continuous distribution was obtained with the ZAP\u201070 stained B\u2010cell threshold. VH mutational status strongly correlated with the optimized control values as 29\/30 low ZAP\u201070 cases had mutated VH genes and 37\/40 high ZAP\u201070 cases used unmutated VH genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Use of an optimized isotypic control threshold could increase the reliability of flow based ZAP\u201070 detection and correlates well with VH mutational status. \u00a9 2011 International Clinical Cytometry Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/cyto.b.20628","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T02:38:01Z","timestamp":1317177481000},"page":"78-84","source":"Crossref","is-referenced-by-count":10,"title":["Improved flow cytometric detection of ZAP\u201070 in chronic lymphocytic leukemia using experimentally optimized isotypic control antibodies"],"prefix":"10.1002","volume":"82B","author":[{"given":"Sergey N.","family":"Preobrazhensky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Szankasi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Bahler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,10,26]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041720"},{"key":"e_1_2_6_3_2","volume-title":"WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues","author":"Swerdlow SH","year":"2008"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1840"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1848"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.4.1177.h81602001177_1177_1184"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.11.1625"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.11.1639"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00753.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1309\/230199FLE32ATUB0"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20137"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20184"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20121"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040857"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1531"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00082-7"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526355"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPPAG4VR4IPGHZ"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20378"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2010.090091"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-299321"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.20127"},{"key":"e_1_2_6_23_2","first-page":"1","volume-title":"Immunophenotpying","author":"Stewart CC","year":"2000"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(19981215)34:6<280::AID-CYTO6>3.0.CO;2-H"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPQS4OXJJSZ5KN"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06928.x"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-184853"}],"container-title":["Cytometry Part B: Clinical Cytometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcyto.b.20628","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.b.20628","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T13:26:02Z","timestamp":1700573162000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cyto.b.20628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,26]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1002\/cyto.b.20628"],"URL":"https:\/\/doi.org\/10.1002\/cyto.b.20628","archive":["Portico"],"relation":{},"ISSN":["1552-4949","1552-4957"],"issn-type":[{"value":"1552-4949","type":"print"},{"value":"1552-4957","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,26]]}}}