ZAP-70, IgVh, and cytogenetics for assessing prognosis in chronic lymphocytic leukemia

Trojani, Alessandra; Montillo, Marco; Nichelatti, Michele; Tedeschi, Alessandra; Colombo, Chiara; Veronese, Silvio; Mura, Maria Angela; Ricci, Francesca; Scarpati, Barbara; Colosimo, Anna; Lodola, Milena; Morra, Enrica

doi:10.3233/cbm-2009-0114

Cited by 16 publications

(11 citation statements)

References 32 publications

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“…In this study, BrcA1 overexpression is associated with crc patients with deeper tumor invasion earlier cancer stage (T3+T4) with statistical significance. ZAp-70 expression has been associated with disease progression in patients with chronic lymphocytic lymphoma (51). In the present study, ZAp-70 overexpression is associated with crc patients with well and moderate differentiated histology.…”

Section: Discussionsupporting

confidence: 62%

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

Tok

2011

Oncol Rep

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Abstract. radiotherapy is increasingly used in adjuvant approaches for colorectal cancer (crc) to reduce local recurrence and improve survival. However, the principal limitation is the large variability in response among different individuals due to tumor heterogeneity. In the present study, we compared gene expression profiles between radiosensitive and radioresistant colorectal cancer cell lines to identify radiation-related molecules that can be used to evaluate the effects of radiation. the crc cell line sW620 was irradiated with a high-energy photo beam. Following radiation treatment, rnA was extracted from non-irradiated and irradiated cells, respectively, and gene expression analysis was performed by oligonucleotide microarray and the DAVID bioinformatics method. to further confirm the results, an additional 4 crc cell lines, colo205, t84, Hct116, sW480 and sW403 were purchased from Atcc. the radiosensitivities of each were determined by the survival fraction at 2 gray (sF2) of the surviving cells using the Atplite assay, and the gene expression profiles after irradiation among the radiosensitive and radioresistant cell lines were analyzed by membrane arrays. the relationships between gene expression and patient clinicopathological features were also analyzed using membrane arrays and rt-pcr. the results from oligonucleotide microarray analysis show that 1601 genes were up-regulated (gene expression ratio of post-to preradiation treatment >2). By bioinformatic database analysis, 30 up-regulated genes were identified as involved in DNA damage response pathways, immune response pathways and the complement and coagulation cascades pathway. Fifteen genes showed differential gene expression profiles between radiosensitive (Hct116 and sW620) and radioresistant crc cell lines (sW403 and sW480). In 110 crc tissues, we detected five genes CDC25A, VAV1, TP73, BRCA1 and ZAP70 from 15 overexpressed genes that significantly related to prognostic factors (tumor size, advanced stage, invasive depth, lymph node metastasis and differentiation). these findings suggest that cDc25A, VAV1, tp73, BrcA1 and ZAp70 may be novel markers for predicting the effectiveness of radiotherapy in crc patients.

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Section: Discussionsupporting

confidence: 62%

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

Tok

2011

Oncol Rep

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“…Recently, there has been an effort to identify new prognostic factors in B-CLL since it is possible that patients in an early stage and who are likely to progress could benefit by being treated immediately before progression occurs. Novel biological markers, such as immunoglobulin heavy chain variable region mutation status (IgVH), CD38 levels, and ZAP-70 expression, can predict treatment requirement and may be helpful for B-CLL management (38)(39)(40). However, we were unable to find a significant modification of oxidative stress in patients with poor prognostic markers of disease.…”

Section: Cancer Investigationmentioning

confidence: 81%

Relationship Between Advanced Oxidation Protein Products, Advanced Glycation End Products, andS-Nitrosylated Proteins With Biological Risk and MDR-1 Polymorphisms in Patients Affected by B-Chronic Lymphocytic Leukemia

Gangemi¹,

Allegra²,

Aguennouz³

et al. 2012

Cancer Investigation

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The aim of our study was to analyze the serum levels of advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs), and protein nitrosylation in patients with B-chronic lymphocytic leukemia (B-CLL). AOPPs, AGEs, and S-nitrosylated were increased in B-CLL patients. The mutation of IgVH gene, CD 38, and Zap 70 expression were not associated with increased oxidative stress. The mutant 2677GT genotype was found to be associated with higher AGEs levels with respect to wild-type genotype, while as far the C3435T MDR1 polymorphism is concerned, subjects presenting wild-type genotype showed higher values of AOPPs with respect to heterozygous genotype. Our results suggest that B-CLL is associated with oxidative stress.

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“…Cytogenetic abnormalities [5], usually determined by FISH because of the low proliferative rate of CLL, and IGHV mutational status [6,14,19–21] appear to be the most important independent prognostic factors in this disease. IGHV mutational status and cytogenetics also commonly track with one another: 17p deletions and 11q deletions are associated with an unmutated IGHV, while del(13q) is associated with a mutated IGHV [17,20].…”

Section: Discussionmentioning

confidence: 99%

“…All IGHV mutation analyses were performed at a single reference laboratory using cycle sequencing analysis. An IGHV non-homologous sequence of <2% was defined as unmutated (low mutational status), and an IGHV non-homologous sequence of ≥2% was defined as mutated (high mutational status) [14,15,19,20,21]. …”

Section: Methodsmentioning

confidence: 99%

Importance of immunoglobulin heavy chain variable region mutational status in del(13q) chronic lymphocytic leukemia

Gladstone

Swinnen

Kasamon

et al. 2011

Leukemia & Lymphoma

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Among prognostic factors for chronic lymphocytic leukemia (CLL), immunoglobulin heavy chain variable region (IGHV) mutation status and DNA analysis appear to be the most important. However, there is limited clinical outcome information for patients with the favorable-risk del(13q) and poor-risk unmutated IGHV. We retrospectively screened all patients with CLL at our institution between 2004 and June 2010 for del(13q) who also had an IGHV analysis. Unmutated IGHV was found in 38/79 patients; age, Rai stage, prior therapy, and time to evaluation were similar to those for patients with mutated IGHV. Unmutated patients were nearly four times more likely to harbor additional chromosomal aberrations compared to mutated patients (p < 0.001). During a median follow-up of 4.5 years, unmutated patients were more likely to demonstrate Rai stage progression (69% vs. 31%, log-rank p < 0.001) and to receive treatment (5-year cumulative probability of treatment: 65% vs. 32%, p < 0.001). Patients with unmutated CLL also had a shorter overall survival (5-year survival probability: 72% vs. 100%, p < 0.001). When limiting analysis to the 47 patients with del(13q) as a sole chromosomal abnormality, the 13 (28%) unmutated patients were more likely to demonstrate Rai progression (p < 0.001), to receive treatment (P = 0.02), and to have a shorter overall survival (P = 0.13) than the 34 mutated patients. These data suggest that del(13q) conveys an indolent course only in patients with IGHV-mutated CLL.

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ZAP-70, IgVh, and cytogenetics for assessing prognosis in chronic lymphocytic leukemia

Abstract: We assessed that IgVh mutational status, ZAP-70 protein and 6q- are powerful prognostic markers. Analyses of all these factors revealed that 11q deletion was the strongest predictor of disease progression in B-CLL.

Cited by 16 publications

References 32 publications

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

Relationship Between Advanced Oxidation Protein Products, Advanced Glycation End Products, andS-Nitrosylated Proteins With Biological Risk and MDR-1 Polymorphisms in Patients Affected by B-Chronic Lymphocytic Leukemia

Importance of immunoglobulin heavy chain variable region mutational status in del(13q) chronic lymphocytic leukemia

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