Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia

Principe, Maria Ilaria Del; Poeta, Giovanni Del; Buccisano, Francesco; Maurillo, Luca; Venditti, Adriano; Zucchetto, Antonella; Marini, Rita; Niscola, Pasquale; Consalvo, María Antonietta Irno; Mazzone, Carla; Ottaviani, Licia; Paterini, Paola; Bruno, Antonio; Bomben, Riccardo; Suppo, Giovanna; Degan, Massimo; Gattei, Valter; Fabritiis, Paolo de; Cantonetti, Maria; Coco, Francesco Lo; Principe, Domenico Del; Amadori, Sergio

doi:10.1182/blood-2005-12-4986

Cited by 180 publications

(202 citation statements)

References 35 publications

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“…8 Here, we described a decrease of T regs in B-CLL patients treated with THAL whose therapeutical anti-TNF effect is known. The effects of TNF might be opposite in patients with RA and CLL, indicating that different mechanisms might be involved in the regulation of the T regs function.…”

mentioning

confidence: 99%

Are surrogates of IGHV gene mutational status useful in B-cell chronic lymphocytic leukemia? The example of Septin-10

Benedetti

Bomben

et al. 2007

Leukemia

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arthritis (RA) upregulated the function of T regs . 8 Here, we described a decrease of T regs in B-CLL patients treated with THAL whose therapeutical anti-TNF effect is known. The effects of TNF might be opposite in patients with RA and CLL, indicating that different mechanisms might be involved in the regulation of the T regs function.In summary, we found a high frequency of T regs in B-CLL patients in this study. The percentage of FOXP3 þ T regs was augmented along with the stage of disease. A therapy combining THAL and FLU reduced the number of T regs . Interestingly, the treatment with THAL resulted in the strongest reduction of T regs when compared with the overall lymphocyte population.

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mentioning

confidence: 99%

Are surrogates of IGHV gene mutational status useful in B-cell chronic lymphocytic leukemia? The example of Septin-10

Benedetti

Bomben

et al. 2007

Leukemia

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“…The levels of ZAP-70 observed in our reporting system (negative, positive, and intermediate) is also reported in the literature with respect to CD38 levels and may represent a continuum as noted by other groups (4,5,(16)(17)(18)(19)(20). This finding would be best addressed in a clinical trials setting by following the ''intermediate'' patients to see whether they convert to a positive state.…”

Section: Discussionmentioning

confidence: 76%

A standardized ZAP‐70 assay—Lessons learned in the trenches

Shults

Miller²,

Davis³

et al. 2006

Cytometry Part B Clinical

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Background: The disease of chronic lymphocytic leukemia (CLL) has been shown to exhibit varying clinical outcomes based on reported laboratory parameters. One of these parameters involves the measurement of the protein levels of zeta-associated protein (ZAP-70) in CLL cells. A standardized assay has not yet reached consensus in the clinical cytometry community.Methods: We developed a system using the 8-peak Rainbow beads as our fluorescence calibrator along with a fixed cell control. Using a panel of CD19-PE, CD5-FITC, and ZAP-70-Alexa 647, we stained normal whole blood, and blood and bone marrow from patients with CLL to determine the level of ZAP-70 expression in T-cell, B-cell, and CLL-cell populations. ZAP-70 expression was reported in molecules equivalent fluorescence (MEFL) based on the calibration of the flow cytometer with the 8-peak Rainbow beads.Results: Daily assay performance as well as operating MEFL defined ranges for ZAP-70 detection in CLL were developed. A rank-order, nonparametric approach to reference ranges was used to assign a cutoff for ''negative'' as well as ranges for ''intermediate'' and ''positive'' staining using T and B cells from a pool of 50 normal subjects, and CLL cells from 395 patients. The assay was validated in a multi-institutional study and has demonstrated correlation with published techniques. Since its initial development, the assay has been implemented at two additional laboratory sites and has been shown to produce reproducible, correlated data at all sites.Conclusions: Strict adherence to standardization can yield an assay that is predictable, reliable, and reproducible as well as capable of multisite implementation. The Rainbow beads provide a common platform for system calibration. The fixed cell culture controls provide a common target to test antibody. The final level of control tests the sensitivity of ZAP-70 detection in a normal peripheral blood sample stained along with the submitted CLL patients. The acceptance/rejection of test results must meet all three levels of control before patient results are reported. q

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“…Previous studies have shown a significant split in the Kaplan-Meier curves at 20% when ZAP-70 expression was related to time to initial treatment (24)(25)(26)(27)(28)39,41).…”

Section: Considerations For the Measurement Of Zap-70mentioning

confidence: 99%