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miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities

Leukemia volume 23, pages 1159–1163 (2009)Cite this article

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world and is characterized by a highly variable clinical course. CLL can be classified into two biological subtypes, according to the presence or absence of somatic mutations in the immunoglobulin heavy-chain variable region (IgVH). IgVH mutational status is of high-clinical relevance: cases with unmutated IgVH show a less favorable course with a rapid progression, whereas cases with mutated IgVH show a stable disease and longer survival. Unfavorable prognosis is also associated with the inactivation of an important tumor-suppressor p53; these patients harbor a deletion of 17p13 and this chromosomal abnormality is often accompanied by the mutation of the second TP53 allele, which leads to the complete elimination of p53 function. Moreover, a single mutation of one of the TP53 allele also occurs in a significant proportion of CLL cases. Patients with TP53 abnormalities typically do not respond to therapy and have a median survival of less than 3 years.

MicroRNAs (miRNAs) are short ∼22 nucleotide long RNA molecules that function as specific regulators of the gene expression with an essential role in cell proliferation, differentiation, apoptosis, chromosome structure and virus resistance. These highly conserved RNAs constitute more than 700 miR genes in the human genome and are supposed to regulate 20–30% of protein-coding genes. miRNAs are associated with RNA-induced silencing complex (RISC), which has been previously proven to repress the translation of the mRNA by an RNA interference mechanism. Many studies have shown that miRNAs are aberrantly expressed in cancer cells, suggesting that they might act as a novel class of oncogenes or tumor suppressors. The first evidence of the involvement of miRNAs in chronic lymphocytic leukemia came from molecular studies, which characterized the 13q14 deletion. Two miRNA genes (miR-15a and miR-16-1), which regulate Bcl2, are the candidate genes located in the 13q14.3 region.1 Several recent publications have defined the miRNA expression profiles in different CLL subtypes: mutated IgVH vs unmutated IgVH and ZAP-70+ vs ZAP-70− cases.1 Although, this data did indeed demonstrate the involvement of miRNAs in CLL pathogenesis, their role in aggressive CLL, bearing TP53 abnormalities, has not yet been clearly defined. Therefore, we have focused on the identification of miRNAs abnormally expressed in CLL cells, which harbor a deletion and/or mutation of the p53 gene (TP53).

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Acknowledgements

We acknowledge Prof Ivo Slapak (Department of Paediatric Otorhinolaryngology) for providing control samples after tonsillectomy, Dr Hana Skuhrova Francova (Center of Molecular Biology and Gene Therapy) for performing IgVH status analysis and Professor Petr Kuglik (Department of Medical Genetics) for FISH data. This work was supported by Research Grant IGA MZ CR NR9293-3/2007 provided by the Internal Grant Agency of the Ministry of Health in the Czech Republic.

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  1. Department of Internal Medicine–Hematooncology, Center of Molecular Biology and Gene Therapy, University Hospital Brno and Medical Faculty MU, Brno, Czech Republic

    M Mraz, K Malinova, J Kotaskova, S Pavlova, B Tichy, J Malcikova, K Stano Kozubik, Y Brychtova, M Doubek, M Trbusek, J Mayer & S Pospisilova

  2. Department of Pathology, University Hospital Brno, Brno, Czech Republic. E-mail: sarka.pospisilova@fnbrno.cz,

    J Smardova

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Mraz, M., Malinova, K., Kotaskova, J. et al. miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities. Leukemia 23, 1159–1163 (2009). https://doi.org/10.1038/leu.2008.377

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