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Updated: May 18, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Differential gene expression profile associated to apoptosis induced by dexamethasone in CLL cells according to
Maria Joao Baptista1, Ana Muntañola, Eva Calpe
1Laboratory of Experimental Hematology, Department of Hematology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Purpose:
Glucocorticoids are part of the therapeutic armamentarium of chronic lymphocytic leukemia (CLL) where it has been suggested that cells with unmutated IGHV genes exhibit higher sensitivity. The mechanisms by which glucocorticoids are active in CLL are not well elucidated. We aimed to ascertain the activity of dexamethasone in CLL cells according to prognosis and to identify the molecular mechanisms that are influencing the response to this drug.
Experimental Design:
Sensitivity to dexamethasone was analyzed ex vivo in 50 CLL and compared according to IGHV mutational status and/or ZAP-70 expression. The response was further compared by gene expression profiling (GEP) of selected cases. Expression of genes of interest was validated by quantitative reverse transcriptase PCR.
Results:
Response to dexamethasone was higher in cases with unmutated IGHV/high ZAP-70 expression, and the levels of induction of the pro-apoptotic Bim protein correlated with the degree of cell death. GEP analysis showed few genes differentially expressed after dexamethasone treatment between mutated and unmutated cases. However, functional annotation analysis showed that unmutated cases had significant enrichment in terms related to apoptosis. Specific analysis of genes of interest conducted in a large series disclosed that in unmutated IGHV cells, FKBP5 expression was higher at baseline and after dexamethasone exposure and that GILZ was more induced by dexamethasone treatment in these cases.
Conclusions:
Unmutated IGHV/high ZAP-70 CLL cells exhibit better response to dexamethasone treatment, which is accompanied by a differential expression of genes involved in the glucocorticoid receptor pathway and by an increased induction of genes related to apoptosis.
