Association of Expression and Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia.

BACKGROUND

In chronic lymphocytic leukemia (CLL), apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the family members play a central role.

AIM

The aim of this study was to investigate the association of pro-apoptotic gene expression and ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase () gene expression.

METHODS

We analyzed the expression of mRNA and mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction.

RESULTS

We detected significant gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated ratio (p=<0.001). Regarding the association with prognostic markers, the ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level expression was associated with -positive status (p=0.035). Both the expression of and ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance.

CONCLUSIONS

Our results suggest that dysregulated expression of and , which leads to a high ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.