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Correlation of flow cytometrically determined expression of ZAP‐70 using the SBZAP antibody with IgVH mutation status and cytogenetics in 1,229 patients with chronic lymphocytic leukemia
Author(s) -
Kern Wolfgang,
Dicker Frank,
Schnittger Susanne,
Haferlach Claudia,
Haferlach Torsten
Publication year - 2009
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.20483
Subject(s) - somatic hypermutation , clone (java method) , cd38 , chronic lymphocytic leukemia , flow cytometry , cytogenetics , microbiology and biotechnology , somatic evolution in cancer , medicine , biology , antibody , gastroenterology , immunology , leukemia , gene , b cell , genetics , cancer , cd34 , chromosome , stem cell
Background: ZAP‐70 provides an important prognostic information in chronic lymphocytic leukemia (CLL); however, the most appropriate antibody clone and way of analysis have not yet been defined. Methods: We determined ZAP‐70 expression in 1,229 patients with CLL using the SBZAP clone by applying three different ways of analysis (% positive B‐cells, mean fluorescence intensity (MFI) in B‐cells, MFI ratio T‐cells:B‐cells). Results: ZAP‐70 expression was related to somatic hypermutation status of IgVH genes for all three ways of analysis ( P < 0.0001 each). The strongest correlation was found for MFI ratio ( r = −0.475, P < 0.0001); cases with mutated and unmutated IgVH status significantly differed in their mean MFI ratio (6.33 vs. 3.34, P < 0.0001). ZAP‐70 expression was weaker in sole del(13q) (5.44 vs. 4.44, P = 0.001) and stronger in del(11q) (3.31 vs. 5.29, P < 0.0001) and del(6q) (3.29 vs. 5.18, P = 0.005). MFI ratio was significantly related to time to therapy ( P = 0.004, RR = 0.79) in 221 evaluable cases. Multivariate analysis proved MFI ratio ( P = 0.043, RR = 0.64) and CD38 ( P = 0.047, RR = 1.20 per 10%) as only parameters independently related to time to therapy. Conclusions: Determination of ZAP‐70 expression using SBZAP and applying MFI ratio T‐cells:B‐cells results in significant relations to IgVH mutation status, cytogenetics, and outcome and should be further analyzed and considered for routine application in CLL. © 2009 Clinical Cytometry Society