ZAP70 in B-CLL cells related to the expression in NK cells is a surrogate marker for mutational status

Wiggers, Tom G. H.; Westra, Guus; Westers, Theresia M.; Abbes, A. P.; Strunk, Annuska; Kuiper-Kramer, Ellen; Poddighe, Pino J.; Loosdrecht, Arjan A. van de

doi:10.1002/cyto.b.21132

Cited by 12 publications

(5 citation statements)

References 20 publications

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“…Majority of the centers in LMICs do not further differentiate their CLL patients based on this criterion and might possibly lump both patient groups together. None of the patients were placed on fludarabine or rituximab, both of which, though considered standard of care22, are quite expensive and cannot be afforded by most patients in LMICs. The median duration of follow-up was 4 months and this portrays the lack of adequate documentation and patient tracking systems.…”

Section: Discussionmentioning

confidence: 99%

“…In the past chlorambucil with or without steroids was the gold standard for management of CLL9. This was been replaced by more efficient combinations involving the use of bendamustine, fludarabine, cladribine, alemtuzumab (recombinant anti-CD52) and rituximab (anti-CD20 monoclonal antibody)22. However, these current first line drugs are quite expensive and not easily available in the economically disadvantaged parts of the world where treatment is largely still chlorambucil/cyclophosphamide-based.…”

Section: Introductionmentioning

confidence: 99%

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Presenting features and treatment outcomes of chronic lymphocytic leukaemia in a resource poor Southern Nigeria

et al. 2019

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Background Chronic lymphocytic leukaemia is a relatively common haematological malignancy affecting older adults, accounting for about 20% of haematological malignancies in Nigeria. Diagnosis of this disease depends on the demonstration of clonal lymphocytosis > 5 × 109/L with a characteristic immunophenotypic pattern amidst other clinical and laboratory features. Objectives To determine the predominant clinical and laboratory features of CLL at presentation and their relationship with patient survival. This study also aims at examining the relationship between treatment protocol and outcome. Methods This is a retrospective study with 8 years data (2010–2018) collected from four different centers. Data was analyzed using SPSS 20.0. Results There were a total of 97 cases, with a male: female ratio of 1.1:1. The median age at presentation was 59 years. Approximately 55% of the patients presented at Binet stage C, with splenomegaly in 93.2% and 78% were anaemic. The mean white cell count was 137.9 ± 14.7 × 109/L, with a median absolute lymphocyte count of 86 × 109/L. The commonest treatment regimen was chlorambucil and prednisolone and males had a superior response. The number of chemotherapy cycles, serum alkaline phosphatase and aspartate transaminase correlated positively with duration of survival. Mortality rate over the five year period was 14.3%. Conclusion CLL was found to present in younger patients when compared to previous studies with a median age of 57 years at diagnosis. Our study showed a slight female preponderance and better response to therapy in males. Majority of the patients presented in Binet stage C and were treated with chlorambucil-based drug combinations compared to more current treatment with Fludarabine-based combinations. A high serum alanine transaminase and alkaline phosphatase was found to positively correlate with survival amongst this patient population

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Presenting features and treatment outcomes of chronic lymphocytic leukaemia in a resource poor Southern Nigeria

et al. 2019

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“…Another example is the ZAP70 expression analysis by flow cytometry, which has been largely abandoned due to difficulties in standardization [ 40 ] [ 41 ] or the ZAP expression analysis by RT-PCR, which requires purification of B cells prior to the assay [ 39 ], rendering this approach unsuitable for routine diagnostics.…”

Section: Discussionmentioning

confidence: 99%

Developing Molecular Signatures for Chronic Lymphocytic Leukemia

et al. 2015

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Chronic lymphocytic leukemia (CLL) is a clonal malignancy of mature B cells that displays a great clinical heterogeneity, with many patients having an indolent disease that will not require intervention for many years, while others present an aggressive and symptomatic leukemia requiring immediate treatment. Although there is no cure for CLL, the disease is treatable and current standard chemotherapy regimens have been shown to prolong survival. Recent advances in our understanding of the biology of CLL have led to the identification of numerous cellular and molecular markers with potential diagnostic, prognostic and therapeutic significance. We have used the recently developed digital multiplexed gene-expression technique (DMGE) to analyze a cohort of 30 CLL patients for the presence of specific genes with known diagnostic and prognostic potential. Starting from a set of 290 genes we were able to develop a molecular signature, based on the analysis of 13 genes, which allows distinguishing CLL from normal peripheral blood and from normal B cells, and a second signature based on 24 genes, which distinguishes mutated from unmutated cases (LymphCLL Mut). A third classifier (LymphCLL Diag), based on a 44-gene signature, distinguished CLL cases from a series of other B-cell chronic lymphoproliferative disorders (n = 51). While the methodology presented here has the potential to provide a "ready to use" classification tool in routine diagnostics and clinical trials, application to larger sample numbers are still needed and should provide further insights about its robustness and utility in clinical practice.

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“…ZAP-70 positive patients have an aggressive course, an immediate treatment requirement, and lower survival rates. If ZAP-70 expression is present, it remains constant all over the clinical course of the patient, and consequently, it is a valid risk marker regardless of the evaluation's timing [7,8].…”

Section: Introductionmentioning

confidence: 99%

Value of Serum Interleukin-22 in Patients With Chronic Lymphocytic Leukemia and Its Relation to Disease Characteristics

Elmeligy,

Sultan,

Ghanem

et al. 2023

Journal of the Medical Research Institute

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Background: Chronic lymphocytic leukaemia (CLL) is a common type of leukaemia characterized by progressive accumulation of monoclonal B cells. The survival and proliferation of CLL cells are stimulated by T-helper cytokines and could be correlated with disease progression. The aim of this study is to assess the value of serum interleukin-22 in patients with chronic lymphocytic leukemia and its relation to disease characteristics. Methods: The study was carried out on 40 CLL patients (newly diagnosed) and 10 healthy controls. Routine hematological and laboratory investigations were performed for all subjects in addition to interleukin-22 (IL-22) level and ZAP-70 expression. Results: Mean values of IL-22 level among CLL patients were significantly higher than in the control group. IL-22 mean values were significantly higher in patients with positive ZAP-70 expression. Moreover, there was a significant positive correlation between serum IL-22 level and ZAP-70. According to the ROC curve, the area under the curve was statistically significant (AUC=0.809 p=0.001). Conclusion: IL-22 & ZAP-70 could act in alliance to maintain survival of CLL cells and its proliferation and could be used as diagnostic as well as prognostic markers. Our findings strongly recommend the incorporation of IL-22 level into routine CLL work up.

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ZAP70 in B-CLL cells related to the expression in NK cells is a surrogate marker for mutational status

Cited by 12 publications

References 20 publications

Presenting features and treatment outcomes of chronic lymphocytic leukaemia in a resource poor Southern Nigeria

Presenting features and treatment outcomes of chronic lymphocytic leukaemia in a resource poor Southern Nigeria

Developing Molecular Signatures for Chronic Lymphocytic Leukemia

Value of Serum Interleukin-22 in Patients With Chronic Lymphocytic Leukemia and Its Relation to Disease Characteristics

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