Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Identification of prognosticators for Binet A chronic lymphocytic leukemia is important for selecting patients with dismal prognosis. We analyzed CD49d expression in 140 consecutive Binet A chronic lymphocytic leukemia. At diagnosis, CD49d >or=30% (54/140, 38.6%) associated with proliferation markers, namely CD38 >or=30% (p=3.9 x 10(-6)), LDH (p=0.007) and beta2-microglobulin (p=0.020). Univariate log-rank analysis identified CD49d >or=30% as a risk factor of treatment free survival (p=8.3 x 10(-5)), time to progression to a more advanced stage (p=4.7 x 10(-4)), and time to lymphocyte doubling (p=0.009). Multivariate analysis selected CD49d >or=30% as an independent treatment free survival predictor after adjustment for biological (HR 2.28; 95% CI 1.71-4.45, p=0.015) and both biological and clinical variables analyzed together (HR 3.33, 95% CI 1.61-6.90, p=0.001). Within Binet A subgroups harboring favorable biological variables (IGHV homology <98%, favorable karyotype, CD38 <30%, ZAP70 <20%) or clinical variables, CD49d >or=30% consistently identified a subset of patients with short treatment free survival. Our observations indicate CD49d >or=30% as a new marker for the initial prognostic assessment of Binet A chronic lymphocytic leukemia.
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PMID:CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia. 1948 61

Plasmoblastic lymphoma (PBL) is a subtype of the diffuse large B-cell lymphoma, typically present as extranodal disease associated with human immune deficiency virus (HIV) infection. PBLs are often the initial manifestation of AIDS. Here we present a case of PBL concerning the oral cavity. A 34-year-old woman presented a tumor in the oral cavity that involved the maxilla and gingiva (confirmed by CT-scan). The gingival biopsy showed a massive infiltration by large lymphoid cells with round, vesicular nuclei, prominent nucleoli, fine chromatin and an significant amount of basophilic cytoplasm which express CD79a, CD138, cytoplasmic lambda light chain and LCA, without staining for CD20, CD38, CD3 and CTK. Serological analysis confirmed HIV positivity. PBLs lack most B-lineage markers, but many express CD79a in at least some of the cells, therefore generate difficulties in differential diagnosis. Overall assessment and correlation of the histopathological and immunohistochemical features with the clinical findings and serology investigation are the most helpful diagnostic tools and can lead to the final diagnosis.
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PMID:Plasmoblastic lymphoma associated with human immunodeficiency virus. 1875 34

Chronic lymphocytic leukemia results from a proliferation/accumulation of monoclonal B lymphocytes. The diagnosis is easily made on blood cytology and immunophenotype. The complexity of mechanisms which govern the clonal evolution translate in a large pronostic diversity on long-term outcome, with a life expectancy ranging from a few years to more than 25 years in the most indolent forms. Prognostic appraisal is currently based on clinical and hematological presentation, whereas cytogenetics, immunoglobulin gene status, expression of proteins involved in cell proliferation such as ZAP70 or CD38 provide more precise but non routine indications. Although there is a lot of effective drugs against the clonal process, any of them are curative, and long term benefit of treatment tailored on individual prognostic features still deserves further studies. Therefore, current treatment recommendations aim at sustaining quality of life in elderly patients, whereas response quality and length are the main targets in younger ones.
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PMID:[Chronic lymphocytic leukemia]. 1915 99

Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgV(H) mutational status, widely differing clinical courses were revealed. Since IgV(H) sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgV(H) mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome-1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgV(H) mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High Cryptochrome-1 expression correlated with IgV(H) unmutated samples. In addition, Cryptochrome-1 was a valuable predictor of disease progression in early-stage chronic lymphocytic leukemia, therefore it can be introduced in clinical practice with the advantage of a simplified method of quantification.
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PMID:Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia. 1918 92

It is well known that translocation between chromosomes 2 and 8, t(2;8)(p12;q24), has a strong association with Burkitt's lymphoma. It has rarely been seen in indolent lymphoproliferative disorders. In this study, we report for the first time on 2 cases of chronic lymphocytic leukemia (CLL) with t(2;8). They were diagnosed as having typical CLL (case 1) and CLL/prolymphocytic leukemia (case 2), respectively, based on morphology and immunophenotyping. Karyotypic analysis of the bone marrow cells using the R-banding technique revealed a karyotype of 47,XY, t(2;8)(p12;q24), +4,[17]/46, XY[9] in case 1 and a karyotype of 45,X, t(Y;7)(q12;q21),t(2;8)(p12; q24),del(12)(p12),-17[5]/46,XY[9] in case 2. T(2;8) translocation was confirmed by whole chromosome painting. Rearrangement of the MYC gene and loss of one p53 allele were detected by FISH only in case 2. Both cases had negative ZAP70 and CD38 expressions; however, only case 1 showed good response to therapy. We consider that MYC rearrangement, loss of one p53 allele as well as other factors, such as more prolymphocytes in the blood and bone marrow and complex chromosome abnormalities, also had adverse effects on the poorer prognosis of case 2.
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PMID:Translocation t(2;8)(p12;q24) in two patients with B Cell chronic lymphocytic leukemia. 1924 86

Fc receptor-like 2 (FCRL2) is highly expressed on B-cell chronic lymphocytic leukemia (B-CLL) cells and could possibly influence disease pathogenesis. Therefore, we investigated FCRL2 mRNA expression in a large cohort with 152 CLL patients in order to assess its role in risk prediction in B-CLL. FCRL2 mRNA expression was found to be expressed at considerably higher levels in peripheral blood mononuclear cells (PBMC) of B-CLL patients compared to controls (range 1.35- to 210-fold upregulation; P < 0.0001) and cells of other hematological diseases. Patients with high FCRL2 expression (according to ROC-analysis) had a significantly longer treatment-free survival (TFS) and overall survival (OS) than patients with low FCRL2 expression (median TFS: 119 vs. 34 months, P < 0.0001; median OS: 321 months vs. not reached, P = 0.009). Univariate comparisons found that FCRL2 expression was weakly associated with IGHV mutation status (P = 0.05), CD38 status (P < 0.0001) and ZAP-70 status (P < 0.0001). Furthermore, we show that the combination of FCRL2 with ZAP70-, CD38- or IGHV-status could further significantly refine the prognostic information provided by either of the factors alone in TFS and OS. In multivariate analysis low FCRL2 expression was a significant independent prognostic factor (HR 2.4; P = 0.005). Here we demonstrate that the level of FCRL2 expression is correlated with prognosis in B-CLL.
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PMID:FCRL2 mRNA expression is inversely associated with clinical progression in chronic lymphocytic leukemia. 1968 11

This study was aimed to detect the telomere length and the telomerase expression activity in patients with chronic lymphocytic leukemia (CLL), and investigate their relation to prognosis of CLL. The telomere length and the telomerase expression activity of peripheral blood and / or bone marrow mononuclear cells were examined by Tel-FISH, a semi-quantitative method and by TRAP-ELISA respectively; the expressions of ZAP70 and CD38 were detected by flow cytometry. The results showed that comparing the telomere length in different stages, there was a tendency that the telomere became prolonged when the stage raised up. There was statistical significant difference between Rai stages III-IV and stage 0, Rai stages III-IV and stages I-II, Binet stage C and stage A, Binet stage C and stage B; while no statistical significant difference existed between Rai stage 0 and stages I-II, Binet stage A and stage B. The telomere length in ZAP70 negative group was found similar as in ZAP70 positive group. The telomere length in CD38 positive group was shorter than that in CD38 negative group, but there was no statistical difference between them. Comparing the telomerase expression activity between different stages, there was a tendency that it increased when the stages went up; comparing the telomerase expression activity at different Rai stages, it increased at the higher stages. One case of CLL demonstrated that telomerase expression did not show at remission stage, but was found at relapse stage, which suggested that telomerase expression may relate to prognosis of disease. It is concluded that the telomerase length is in relation to Rai and Binet stage, which was shorter at higher stage than that at lower stage and intermediate stage. It seemed that the telomerase expression activity increased at higher stages. The expression of telomerase in mononuclear cells is stable and not influenced by treatment.
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PMID:[Telomere length and telomerase expression activity in mononuclear cells of patients with chronic lymphocytic leukemia]. 2003 Sep 16

Exosome vesicles of endocytic origin are involved in communication between tumor and immune cells. In addition, membrane rafts (MR) may support the sorting of proteins associated with exosomes. CD38 is found at the plasma membrane and in recycling endosomes, which are both redistributed toward the immunological synapse (IS) upon T cell antigen receptor (TCR) engagement. The data of this study provide evidence that CD38 is expressed on the surface of secreted exosomes derived from lymphoblastoid B cells. Exosomic CD38 is associated with the signaling molecules CD81, Hsc-70 and Lyn. Likewise, in MR, CD38 is associated with CD81, CD19, Lyn, Galphai-2, Hsc-70 and actin. Therefore, a high degree of overlap in the pattern of signaling proteins associated with CD38 in exosomes and MR exists. Exosomic and MR CD38, by virtue of these interactions, have signaling potential. Indeed, CD38 is enzymatically active in both exosomes and MR, and CD38 ligation induces Akt/PKB and Erk activation, which is accompanied by increased translocation of CD38 into MR. In conclusion, the present study indicates that CD38 localizes to MR, where it promotes cell signaling, and it is exported out of the cells through the exosome-mediated exocytic pathway, where it may act as an intercellular messenger.
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PMID:Exosomes from human lymphoblastoid B cells express enzymatically active CD38 that is associated with signaling complexes containing CD81, Hsc-70 and Lyn. 2057 Jun 73

Many prognostic factors have been identified in chronic lymphocytic leukaemia (CLL). Based on the assessment of B cell receptor (BCR) structure and function, a subdivision into subtypes is possible (e.g., immunoglobulin heavy chain variable gene segment (IGHV) unmutated and mutated, V3-21 usage) with distinct biological and clinical characteristics. Recurrent genomic aberrations (i.e., 11q and 17p deletion) and gene mutations (i.e., TP53 and ATM) help to define biological and clinical subgroups. In addition, serum markers (e.g., thymidine kinase (TK) and beta2-microglobulin (beta2-MG)), cellular markers (e.g., CD38 and ZAP70) and clinical staging have an impact on outcome in CLL. The biological characterisation of CLL has not only led to progress in outcome prediction but also has begun to be translated into novel treatment strategies. Nonetheless, most factors associated with prognosis have not been thoroughly interrogated for their predictive value in the light of different therapeutic approaches. With a growing number of agents acting on specific biological targets and being used in different clinical situations, the future is likely to bring the identification of predictive factors in CLL.
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PMID:Moving from prognostic to predictive factors in chronic lymphocytic leukaemia (CLL). 2062 Sep 72

The fludarabine plus cyclophosphamide (FC) regimen was reported to be superior to chlorambucil or fludarabine alone in terms of complete response (CR), overall response (OR) and progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukaemia (CLL). In the present study, we compared the efficacy and toxicity of FC administered through oral and intravenous route in 65 untreated patients affected by advanced CLL. No statistical differences were noticed between the two routes of administration in terms of OR, PFS, time to re-treatment (TTR) and overall survival (OS) of analysed patients. We also assessed the influence on the clinical outcome of the mutation status of the immunoglobulin variable region heavy chain (IgVH) gene, of the cytogenetic abnormalities and of the expression of ZAP70 and CD38 in patients' primary samples. Among the 58 evaluable patients, 31 (53%) achieved a CR and 18 (31%) a partial response. The median PFS was 35 months, median TTR was 42 months and median OS was not reached after 45 months (range, 1-161). A significantly lower OR rate was noticed in patients with high-risk cytogenetic abnormalities (del 17p, del 11q). In this study, high-risk cytogenetic abnormalities and unmutated IgVH genes were independent predictors of TTR. These results underline the importance of biological stratifications in front-line treatment of CLL patients. We confirm that FC is an effective regimen with mild toxicities; it could be recommended for patients with low-risk biological parameters who represent, in our experience, about 30% of the total.
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PMID:Comparison between oral and intravenous fludarabine plus cyclophosphamide regime as front-line therapy in patients affected by chronic lymphocytic leukaemia: influence of biological parameters on the clinical outcome. 2062 2


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