Identification of progression markers in B-CLL by gene expression profiling.

Abstract:

OBJECTIVE:B-cell chronic lymphocytic leukemia is a heterogeneous disease with a pronounced variation in the clinical course. With the purpose of identifying genes that could be related to disease progression, we have performed gene expression profiling on B-CLL patients with an indolent disease and patients with a progressive disease with need for therapy. MATERIALS AND METHODS:we applied the Affymetrix GeneChip technique to 11 B-CLL patients with stable and 10 patients with clinically progressive disease. Supervised and unsupervised clustering methods with different algorithms were used to identify genes that tend to give a distinction between stable and progressive disease. RESULTS:The supervised learning procedures identified groups of genes with a combined power to discriminate samples from progressive and stable disease with 70-90% accuracy. The gene for protein phosphatase 2 regulatory subunit B' (B56) gamma isoform (PPP2R5C) and the gene for retinoblastoma-like 2 (p130) (RBL2) were included among the best discriminators; both genes were downregulated in progressive as compared to stable B-CLL. In a hierarchical clustering analysis based on gene expression pattern three clinical subcategories could be identified: one with a more severe clinical outcome, a second one with good prognosis, and a third one that was intermediate between the other two groups. CONCLUSIONS:Our application of microarray analysis on a clinically well defined material has identified a number of genes with combined expression patterns related to stable or progressive disease in general. Unsupervised clustering suggested the existence of subclasses of samples in the progressive group that may be identifiable through gene expression patterns.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Fält S,Merup M,Gahrton G,Lambert B,Wennborg A

doi

10.1016/j.exphem.2005.05.007

keywords:

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

883-93

issue

8

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(05)00216-X

journal_volume

33

pub_type

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