Bulky lymphadenopathy with poor clinical outcome is associated with ATM downregulation in B-cell chronic lymphocytic leukemia patients irrespective of 11q23 deletion

Avadhut D Joshi; John D Dickinson; Ganapati V Hegde; Warren G Sanger; James O Armitage; Philip J Bierman; Robert G Bociek; Marcel P Devetten; Julie M Vose; Shantaram S Joshi

doi:10.1016/j.cancergencyto.2006.07.010

Bulky lymphadenopathy with poor clinical outcome is associated with ATM downregulation in B-cell chronic lymphocytic leukemia patients irrespective of 11q23 deletion

Cancer Genet Cytogenet. 2007 Jan 15;172(2):120-6. doi: 10.1016/j.cancergencyto.2006.07.010.

Authors

Avadhut D Joshi¹, John D Dickinson, Ganapati V Hegde, Warren G Sanger, James O Armitage, Philip J Bierman, Robert G Bociek, Marcel P Devetten, Julie M Vose, Shantaram S Joshi

Affiliation

¹ Department of Genetics, Center for Research in Leukemia and Lymphoma, University of Nebraska Medical Center, Omaha, NE 68198-6395, USA.

PMID: 17213020
DOI: 10.1016/j.cancergencyto.2006.07.010

Abstract

B-cell chronic lymphocytic leukemia (B-CLL) is the most common B-cell leukemia among older populations in Western countries. The clinical course of B-CLL is heterogeneous: in some patients the disease course is indolent, in others it is aggressive. The B-CLL subgroups with chromosome 11q23 deletion have been associated with aggressive disease course involving ATM deletion, extensive bulky lymphadenopathy (BLA), and inferior clinical outcome. Using real-time reverse transcriptase-polymerase chain reaction, we found that ATM was consistently underexpressed in B-CLL patients with BLA, irrespective of 11q23 deletion status. In addition, B-CLL patients who presented with BLA had a significantly shorter time to treatment (2 months) than did patients without BLA (74 months). Moreover, gene expression analysis in B-CLL patients with and without BLA revealed differences in expression for genes involved in apoptosis, cell cycle, and cell adhesion. These results indicate an association between BLA and reduced expression of ATM, suggesting a role for ATM in disease progression in B-CLL.

MeSH terms

Ataxia Telangiectasia Mutated Proteins
Cell Adhesion / genetics
Cell Cycle / genetics
Cell Cycle Proteins / antagonists & inhibitors
Cell Cycle Proteins / biosynthesis*
Cell Cycle Proteins / genetics*
Chromosome Deletion*
Chromosomes, Human, Pair 11 / genetics*
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / biosynthesis*
DNA-Binding Proteins / genetics*
Down-Regulation / genetics*
Female
Gene Expression Regulation, Leukemic*
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
Lymphatic Diseases / diagnosis
Lymphatic Diseases / genetics*
Lymphatic Diseases / pathology
Male
Middle Aged
Prognosis
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / biosynthesis*
Protein Serine-Threonine Kinases / genetics*
Tumor Suppressor Proteins / antagonists & inhibitors
Tumor Suppressor Proteins / biosynthesis*
Tumor Suppressor Proteins / genetics*

Substances

Cell Cycle Proteins
DNA-Binding Proteins
Tumor Suppressor Proteins
ATM protein, human
Ataxia Telangiectasia Mutated Proteins
Protein Serine-Threonine Kinases