Abstract
MicroRNAs (miRNAs) are small non-coding single-stranded RNA molecules that regulate gene expression at the post-transcriptional level. In the pathogenesis of chronic lymphocytic leukemia (CLL), miR-15a and miR-16-1 play an important role. These miRNAs are located on chromosome 13 in the 13q14.3 region, which is deleted in more than 55% of CLL patients. This aberration affects expression of miRNAs. The study aimed at performing a molecular genetic analysis of miR-15a and miR-16-1 expression in a group of 39 patients diagnosed with CLL and determining the association between the expression of the two miRNAs and types of deletions in the 13q14 region. We used fluorescence in situ hybridiziation (FISH) for determination of mono- or biallelic deletion 13q and quantitative polymerase chain reaction (Q-RT-PCR) to revealed expression miR-15a and miR-16-1 in 39 patients suffering from CLL. The analysis comprised 19 patients with monoallelic 13q14 deletion, 3 patients with biallelic deletion, 9patients with both monoallelic and biallelic deletions, and 8 patients without 13q14 deletion serving as controls. The results showed different levels of miRNA expression in individual patients. Significantly higher normalized levels of miR-15a expression were found in the control group and patients with monoallelic 13q14 expression compared with patients with biallelic deletion. There was a significantly decreased expression of both miRNAs in patients with biallelic deletion of the 13q14 region but only when deletions were present in 77% or more of cells, as detected by fluorescent in situ hybridization (FISH).
Highlights
MicroRNAs are small non-coding single-stranded RNA molecules that regulate gene expression at the post-transcriptional level
This study aimed at determining the relative levels of miR-15a and miR-16-1 expression in a group of chronic lymphocytic leukemia (CLL) patients with deletion of the 13q14 region detected by fluorescent in situ hybridization (FISH) and second, at assessing potential changes in miR15a and miR-16-1 expression with respect to the type of 13q14 deletion present and other prognostically significant parameters
The results showed different levels of miRNA expression in individual patients
Summary
MicroRNAs (miRNAs) are small non-coding single-stranded RNA molecules that regulate gene expression at the post-transcriptional level. In the pathogenesis of chronic lymphocytic leukemia (CLL), miR-15a and miR-16-1 play an important role These miRNAs are located on chromosome 13 in the 13q14.3 region, which is deleted in more than 55% of CLL patients. The study aimed at performing a molecular genetic analysis of miR-15a and miR-16-1 expression in a group of 39 patients diagnosed with CLL and determining the association between the expression of the two miRNAs and types of deletions in the 13q14 region. Chronic lymphocytic leukemia (CLL) is the most common type of hematological malignancy diagnosed in adults in the Western hemisphere. This condition is characterized by the accumulation of mature-looking B cells with CD19+/CD20+/CD23+ immunophenotypes and aberrant expression of the CD5 marker. The prognosis of patients with CLL is determined by various biological parameters, such as immunoglobulin heavy chain variable region (IgVH) mutation status[4,5, 70] kDa zeta‐associated protein (ZAP70) expression[6,7], and cytogenetic changes[8]
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