| AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations. | |
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MedLine Citation:
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PMID: 19898425 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor in its transformation. |
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Authors:
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Mona Leuenberger; Simona Frigerio; Peter J Wild; Franziska Noetzli; Dimitri Korol; Dieter R Zimmermann; Carole Gengler; Nicole M Probst-Hensch; Holger Moch; Marianne Tinguely |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-06 |
Journal Detail:
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Title: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Volume: 23 ISSN: 1530-0285 ISO Abbreviation: Mod. Pathol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-03 Completed Date: 2010-04-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8806605 Medline TA: Mod Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 177-86 Citation Subset: IM |
Affiliation:
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Department of Pathology, Institute of Surgical Pathology, University Hospital, CH-8091Zurich, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Cytidine Deaminase / biosynthesis* DNA Mutational Analysis Female Gene Rearrangement Genes, Immunoglobulin / genetics Humans Immunoglobulin Heavy Chains / genetics Immunoglobulin Variable Region / genetics Immunohistochemistry In Situ Hybridization, Fluorescence Kaplan-Meiers Estimate Leukemia, Lymphocytic, Chronic, B-Cell / enzymology*, genetics*, mortality Male Middle Aged Mutation Prognosis Tissue Array Analysis Tumor Markers, Biological / analysis* |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin Heavy Chains; 0/Immunoglobulin Variable Region; 0/Tumor Markers, Biological; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
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