Zeta-associated protein 70 expression in chronic lymphocytic leukemia: Relevance in Indian context

Background: Chronic lymphocytic leukemia (CLL) is prognosticated using the Rai and the Binet's staging. In the past few years, new parameters have been considered for prognostication. One such marker that has been a subject of speculation and found useful by some western studies is zeta-associated protein 70 (ZAP-70). Aim: To investigate the prevalence of ZAP-70 and find out its association with other prognostic markers like Rai and Binet's stage and CD38 in Indian CLL patients. Materials and Methods: Twenty-nine newly diagnosed cases of CLL were selected over 1 year. Immunophenotyping was done and expression of CD38 and ZAP-70 was evaluated on gated CLL cells. Statistical Analysis: Qualitative data were expressed as frequency and percentage. Differences between groups were evaluated using Student's t-test for quantitative data and Chi-square test/Fisher's exact t-test for qualitative variables. A P value less than 0.05 was considered significant. Results and Conclusion: We found a lower prevalence rate of ZAP-70 (2/29, 6.89%) with no association with any of the conventional poor prognostic factors. A large number of our CLL patients fall into the good prognostic group (22/29, ZAP 70?/CD38?) with a least number in the poor prognostic group (2/29, ZAP-70 + CD38+). Also, no association was found between ZAP-70 and CD38. The findings of the present study suggest that the majority of CLL patients in India have a good prognosis, may not require treatment, and have good overall survival. Geographical variations, genetic makeup, and natural history of the CLL could be the cause of such differences from western literature.

ZAP-70 expression is associated with increased CD4 central memory T cells in chronic lymphocytic leukemia: cross-sectional study

ABSTRACT Background: Although chronic lymphocytic leukemia is basically a B cell disease, its pathophysiology and evolution are thought to be significantly influenced by T cells, as these are probably the most important interaction partner of neoplastic B cells, participating in their expansion, differentiation and survival. Chronic lymphocytic leukemia B cells may also drive functional and phenotypic changes of non-malignant T cells. There are few data about the association between memory T cells and prognosis, especially related to ZAP-70, a common reliable surrogate of the gold standard chronic lymphocytic leukemia prognostic markers. Objective: The aim of this study was to investigate whether the expression of ZAP-70 in chronic lymphocytic leukemia patients is associated with abnormal patterns of the distribution of naïve and memory T cells related to crosstalk between these cells. Methods: In this cross-sectional, controlled study, patients with chronic lymphocytic leukemia were compared with healthy blood donors regarding the expression of ZAP-70 and the distribution of naïve and memory T cell subsets in peripheral blood as measured by flow cytometry. Results: ZAP-70 positive patients presented an increased frequency and absolute number of central memory CD4+ T cells, but not CD8+ T cells, compared to ZAP-70 negative patients and age-matched apparently healthy donors. Conclusions: Because central memory CD4+ T cells are located in lymph nodes and express CD40L, we consider that malignant ZAP-70-positive B cells may receive beneficial signals from central memory CD4+ T cells as they accumulate, which could contribute to more aggressive disease.

Smudge cell percentage as a surrogate marker for ZAP-70 expression in patients with chronic lymphocytic leukemia

BACKGROUND: This study aimed to evaluate the prognostic value of smudge cell percentage as a surrogate marker for zeta-chain-associated protein kinase 70 (ZAP-70) expression in chronic lymphocytic leukemia (CLL) patients. METHODS: Sixty three newly diagnosed CLL patients were investigated at the Hematology Department of the Medical Research Institute of Alexandria University with complete blood count, lactate dehydrogenase, β2 microglobulin levels, ZAP-70 expression, and estimation of the percentage of smudge cells. RESULTS: The percentage of smudge cells ranged from 2 to 58% with a mean of 24.03±13.98%. Higher percentages of smudge cells (>30%) were statistically significantly associated with markers of better prognosis (negative ZAP-70, early-stage disease according to the Binet and Rai staging systems, as well as low and intermediate risk CLL prognostic index). The percentage of smudge cells showed significantly negative correlation with the ZAP-70 expression and higher area under the curve for prediction of ZAP-70 positivity with better survival for 36 months in patients with >30% smudge cells. CONCLUSION: The percentage of smudge cells at presentation of newly diagnosed CLL patients could be used as a surrogate marker for ZAP-70 expression and an additional prognostic marker for disease progression.

Prevalence of ZAP-70 and CD 38 in Indian chronic lymphocytic leukemia patients.

Aim of Study: Chronic lymphocytic leukemia (CLL) is the most common chronic lympho-proliferative disorder. This study was undertaken to know the prevalence of ZAP-70 and CD 38 in the treatment naive patients of CLL seen at a tertiary care centre of north India. Materials and Methods: ZAP-70 and CD 38 were tested by flow cytometry on peripheral blood samples. ZAP-70 positive and CD 38 positivity was defined as positive expression on 20% and 30% of CLL cells, respectively. Clinico-hematological profile and its correlation with ZAP-70 and CD 38 were assessed in consecutive 80 CLL patients. Results: There were 64 males and median age of the group was 58 years. Sixteen patients (20%) were asymptomatic and diagnosed incidentally. Median total lymphocyte count (TLC) at presentation was 62 × 10 9 /L. Rai stage distribution was: Stage 0-6, stage I-20, stage II-36, stage III-5, and stage IV-13. ZAP-70 and CD 38 positivity were detected in 20 patients (25%) and 29 patients (36%), respectively. Eleven patients were positive and 34 were negative for both ZAP-70 and CD 38 yielding a concordance rate of 56%. There was no statistically significant difference between ZAP-70 and CD 38 positivity and negativity with regard to age, sex, Lymphocyte count, lymphadenopathy, organomegaly, and Rai staging. Conclusion: ZAP-70 and CD 38 positivity were detected 25% and 36%, respectively, with concordance rate of 56%, which is higher than Western literature. There was no correlation of ZAP-70 and CD 38 positivity with age, sex, lymphadenopathy, organomegaly, and Rai staging.

Expression of CD38 and ZAP-70 in chronic lymphocytic leukemia patients and their clinical significance / 白血病·淋巴瘤

Objective To investigate the expression of CD38 and ZAP-70 in chronic lymphocytic leukemia and the relationship between the clinical stages and prognostic significance.Methods Flow cytometry was used to analyze CD38 and ZAP-70 expression in CLL,the patients were divided into high-risk group (Ⅲ,Ⅳ stage) (25 cases) and low-medivm risk group (0,Ⅰ,Ⅱ stage) (17 cases) according to Rai clinical stages.The distribution of CD38 and ZAP-70 expression in Rai clinical stages and the prognostic significance were analyzed.Results Positive expression of CD38 was 47.6 ％ (20/42) in all patients,64.0 ％(16/25) patients in high-risk group and 23.5 ％ (4/17) in low-medium risk group.The distribution of CD38 expression had significant difference between two groups (x2 =6.645,P =0.014).Positive expression of ZAP-70 was 40.5 ％ (17/42) in all patients,60.0 ％ (15/25) patients in high-risk group and 11.8 ％ (2/17) in low-medium risk group.The distribution of ZAP-70 expression had significant difference between two groups (x 2 =9.772,P =0.003).The patients with ZAP-70+ CD38 and ZAP-70+ CD38 were more distribute in high risk campare to the CD38+ ZAP-70- in low-medium risk group (x 2=10.076,9.346,6.005,all P ＜ 0.05).Follow-up 48 months (1-136 months),the progression-free survival of patients with ZAP-70+ CD38+ and ZAP-70 CD38 were respectively for 19.0 and 58.0 months (x2 =11.488,P =0.003).The progression-free survival of ZAP-70+CD38 or ZAP-70 CD38+ were 43.5 and 51.7 months and not statistically significant (x2 =0.075, P =0.784).Conclusion CD38 and ZAP-70 positive expression occurs in large proportion of CLL patients with advanced stages (Rai Ⅲ and Ⅳ stage) and according to the clinical stages the expression of CD38 and ZAP-70 may be predicted.The current findings suggest that both ZAP-70 and CD38 expression should be assessed in patients with CLL for the definition of prognostic subgroups.

Expressions of ZAP-70 and CD38 in chronic B lymphocytic leukemia and their clinical significance / 白血病·淋巴瘤

Objective To detect the ZAP-70 and CD38 expression in these patients with chronic B lymphocytic leukemia (B-CLL) and explore their relationship and clinical significance. Methods The expressions of ZAP-70 and CD38 in bone marrow or peripheral blood of 21 patients with B-CLL were detected by flow cytometry. Results ZAP-70 was positively expressed in 9 of all patients, CD38 was positive in 8 of all patients. ZAP-70 and CD38 were both expressed in 8 patients, ZAP-70 and CD38 were none expressed in 8 patients. Conclusion CD38 and ZAP-70 expression can offer important prognostic information. Cases of B-CLL positive for ZAP-70 and CD38 indicate a worse prognosis. There is a good correlation between these new prognostic factors.

Effect of Bromocriptine on the Activation of T Lymphocyte Stimulated by Phytohemagglutinin / 实用儿科临床杂志

Objective To study the effect of bromocriptine(BRC) on the activation of T lymphocyte stimulated by phytohemagglutinin(PHA).Methods After CD4+ T cell line Jurkat E6-1 cells were stimulated by PHA,prolactin(PRL) and BRC,respectively,the expression of linker for activation of T cells(LAT) and zeta-chain T cell receptor associated protein kinase 70 000(ZAP-70) mRNA of T lymphocytes were checked by RT-PCR.The expression of PRL mRNA of T lymphocytes was detected by Real time PCR.The expression of CD25(cluster of differentiation) as a marker of early activation on the surface of T lymphocytes was detected by flow cytometry,and the activation of nuclear factor-?B(NF-?B) was detected by luciferase reporter system.Results 1.BRC inhibited the expression of ZAP-70 as the common signal molecules both in the T lymphocyte activation pathway and PRL-prolactin-prolactin receptor(PRLR) signal transduction pathway,and decreased the expression of PRL mRNA produced by activation T lymphocytes.2.BRC enhanced the expression of LAT mRNA as another important signal molecular on the T lymphocytes and CD25 on the surface of the T lymphocytes.3.The activation of NF-?B of T lymphocytes was decreased.Conclusions BRC might inhibit the activation of T lymphocytes by inhibiting the expression of ZAP-70,the common signal molecules between T lymphocytes activation and PRL-PRL pathway,and PRL mRNA,the like-T lymphocyte growth factor.