11q22.3 deletion in B-chronic lymphocytic leukemia is specifically associated with bulky lymphadenopathy and ZAP-70 expression but not reduced expression of adhesion/cell surface receptor molecules

John D Dickinson, Jamie Gilmore, Javeed Iqbal, Warren Sanger, James C. Lynch, John Chan, Philip Jay Bierman, Shantaram S Joshi

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Abstract

The presence of chromosome abnormalities promotes tumor progression in B-chronic lymphocytic leukemia (CLL). However, the molecular pathways that are relevant to tumor progression remain unclear. In this study, we screened for common chromosome abnormalities [13q14 del, 11q22.3 (ATM) del, 17p13 (p53) del and trisomy 12] by fluorescent in situ hybridization in 40 B-CLL patients. Each of the four chromosome abnormality groups was compared to several clinical factors related to lymphocyte behaviour in CLL. The 11q22.3 (ATM) deletion group was significantly associated with the presence of bulky abdominal/ mediastinal lymphadenopathy (P=0.014). We hypothesized that this phenotype would be associated with an altered transcription pattern of genes. Class comparison analysis by significance analysis of microarrays on a subset of CLL samples (n =14) indicated that a number of cell surface receptor and adhesion related genes were under-expressed in the 11q22.3 deletion group (CD44, CD11a, PTPRC, CD79a, chemokine ligand 17 and chemokine receptor type 6). The presence of additional prognostic factors, such as CD38 and immunoglobulin heavy chain variable region mutational status, may also influence the transcriptional pathways between the two groups. Therefore, we employed a novel analysis technique for the correlation of log 2 gene expression ratios with the percentage of each tumor that carried the 11q22.3 deletion. Using Spearman's correlation, ZAP-70, chemokine ligand 17, BSAP (PAX5), CD7, LAG3 and PTPR6 were significantly correlated with the percentage of cells with the 11q22.3 deletion. However, the down-regulation of cell surface receptors and adhesion molecules observed by class comparison could not be confirmed to be specific for the 11q22.3 deletion by this method.

Original languageEnglish (US)
Pages (from-to)231-244
Number of pages14
JournalLeukemia and Lymphoma
Volume47
Issue number2
DOIs
StatePublished - Feb 1 2006

Fingerprint

Cell Surface Receptors
B-Cell Chronic Lymphocytic Leukemia
Chromosome Aberrations
Chemokines
Ligands
Neoplasms
Immunoglobulin Heavy Chains
Chemokine Receptors
Trisomy
Microarray Analysis
Fluorescence In Situ Hybridization
Genes
Down-Regulation
Lymphocytes
Phenotype
Gene Expression
Lymphadenopathy

Keywords

  • CLL
  • Chromosome abnormalities
  • Correlation analysis
  • Gene expression array
  • ZAP-70

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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title = "11q22.3 deletion in B-chronic lymphocytic leukemia is specifically associated with bulky lymphadenopathy and ZAP-70 expression but not reduced expression of adhesion/cell surface receptor molecules",
abstract = "The presence of chromosome abnormalities promotes tumor progression in B-chronic lymphocytic leukemia (CLL). However, the molecular pathways that are relevant to tumor progression remain unclear. In this study, we screened for common chromosome abnormalities [13q14 del, 11q22.3 (ATM) del, 17p13 (p53) del and trisomy 12] by fluorescent in situ hybridization in 40 B-CLL patients. Each of the four chromosome abnormality groups was compared to several clinical factors related to lymphocyte behaviour in CLL. The 11q22.3 (ATM) deletion group was significantly associated with the presence of bulky abdominal/ mediastinal lymphadenopathy (P=0.014). We hypothesized that this phenotype would be associated with an altered transcription pattern of genes. Class comparison analysis by significance analysis of microarrays on a subset of CLL samples (n =14) indicated that a number of cell surface receptor and adhesion related genes were under-expressed in the 11q22.3 deletion group (CD44, CD11a, PTPRC, CD79a, chemokine ligand 17 and chemokine receptor type 6). The presence of additional prognostic factors, such as CD38 and immunoglobulin heavy chain variable region mutational status, may also influence the transcriptional pathways between the two groups. Therefore, we employed a novel analysis technique for the correlation of log 2 gene expression ratios with the percentage of each tumor that carried the 11q22.3 deletion. Using Spearman's correlation, ZAP-70, chemokine ligand 17, BSAP (PAX5), CD7, LAG3 and PTPR6 were significantly correlated with the percentage of cells with the 11q22.3 deletion. However, the down-regulation of cell surface receptors and adhesion molecules observed by class comparison could not be confirmed to be specific for the 11q22.3 deletion by this method.",
keywords = "CLL, Chromosome abnormalities, Correlation analysis, Gene expression array, ZAP-70",
author = "Dickinson, {John D} and Jamie Gilmore and Javeed Iqbal and Warren Sanger and Lynch, {James C.} and John Chan and Bierman, {Philip Jay} and Joshi, {Shantaram S}",
year = "2006",
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T1 - 11q22.3 deletion in B-chronic lymphocytic leukemia is specifically associated with bulky lymphadenopathy and ZAP-70 expression but not reduced expression of adhesion/cell surface receptor molecules

AU - Dickinson, John D

AU - Gilmore, Jamie

AU - Iqbal, Javeed

AU - Sanger, Warren

AU - Lynch, James C.

AU - Chan, John

AU - Bierman, Philip Jay

AU - Joshi, Shantaram S

PY - 2006/2/1

Y1 - 2006/2/1

N2 - The presence of chromosome abnormalities promotes tumor progression in B-chronic lymphocytic leukemia (CLL). However, the molecular pathways that are relevant to tumor progression remain unclear. In this study, we screened for common chromosome abnormalities [13q14 del, 11q22.3 (ATM) del, 17p13 (p53) del and trisomy 12] by fluorescent in situ hybridization in 40 B-CLL patients. Each of the four chromosome abnormality groups was compared to several clinical factors related to lymphocyte behaviour in CLL. The 11q22.3 (ATM) deletion group was significantly associated with the presence of bulky abdominal/ mediastinal lymphadenopathy (P=0.014). We hypothesized that this phenotype would be associated with an altered transcription pattern of genes. Class comparison analysis by significance analysis of microarrays on a subset of CLL samples (n =14) indicated that a number of cell surface receptor and adhesion related genes were under-expressed in the 11q22.3 deletion group (CD44, CD11a, PTPRC, CD79a, chemokine ligand 17 and chemokine receptor type 6). The presence of additional prognostic factors, such as CD38 and immunoglobulin heavy chain variable region mutational status, may also influence the transcriptional pathways between the two groups. Therefore, we employed a novel analysis technique for the correlation of log 2 gene expression ratios with the percentage of each tumor that carried the 11q22.3 deletion. Using Spearman's correlation, ZAP-70, chemokine ligand 17, BSAP (PAX5), CD7, LAG3 and PTPR6 were significantly correlated with the percentage of cells with the 11q22.3 deletion. However, the down-regulation of cell surface receptors and adhesion molecules observed by class comparison could not be confirmed to be specific for the 11q22.3 deletion by this method.

AB - The presence of chromosome abnormalities promotes tumor progression in B-chronic lymphocytic leukemia (CLL). However, the molecular pathways that are relevant to tumor progression remain unclear. In this study, we screened for common chromosome abnormalities [13q14 del, 11q22.3 (ATM) del, 17p13 (p53) del and trisomy 12] by fluorescent in situ hybridization in 40 B-CLL patients. Each of the four chromosome abnormality groups was compared to several clinical factors related to lymphocyte behaviour in CLL. The 11q22.3 (ATM) deletion group was significantly associated with the presence of bulky abdominal/ mediastinal lymphadenopathy (P=0.014). We hypothesized that this phenotype would be associated with an altered transcription pattern of genes. Class comparison analysis by significance analysis of microarrays on a subset of CLL samples (n =14) indicated that a number of cell surface receptor and adhesion related genes were under-expressed in the 11q22.3 deletion group (CD44, CD11a, PTPRC, CD79a, chemokine ligand 17 and chemokine receptor type 6). The presence of additional prognostic factors, such as CD38 and immunoglobulin heavy chain variable region mutational status, may also influence the transcriptional pathways between the two groups. Therefore, we employed a novel analysis technique for the correlation of log 2 gene expression ratios with the percentage of each tumor that carried the 11q22.3 deletion. Using Spearman's correlation, ZAP-70, chemokine ligand 17, BSAP (PAX5), CD7, LAG3 and PTPR6 were significantly correlated with the percentage of cells with the 11q22.3 deletion. However, the down-regulation of cell surface receptors and adhesion molecules observed by class comparison could not be confirmed to be specific for the 11q22.3 deletion by this method.

KW - CLL

KW - Chromosome abnormalities

KW - Correlation analysis

KW - Gene expression array

KW - ZAP-70

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