MicroRNA in CLL

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Semin Oncol. 2006 Apr;33(2):167-73. Related Articles, Links

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Genomics of Chronic Lymphocytic Leukemia MicroRNAs as New Players

With Clinical Significance.

Calin GA, Croce CM.

Department of Molecular Virology, Immunology and Medical Genetics

and Comprehensive Cancer Center, Ohio State University, Columbus, OH.

Chronic lymphocytic leukemia (CLL), the most frequent leukemia in

adults in the Western world, is characterized by predominantly

nondividing malignant CD5(+) B cells overexpressing the anti-apoptotic

Bcl2 protein.

Significant familial aggregation with largely unknown mode of

inheritance has been demonstrated. Until recently little else was

known regarding the events leading to CLL initiation and progression.

New findings support the view that CLL is a genetic disease where the

main alterations occur at the level of

transcriptional/post-transcriptional regulation of the malignant cells

genome because of deregulations of a new class of genes named

microRNAs (miRNAs).

miRNA genes miR-15a and miR-16-1, located at 13q14.3, are frequently

deleted and/or downregulated in patients with B-cell CLL.

Both microRNAs negatively regulate Bcl2 at a post-transcriptional

level and this repression is enough to induce apoptopsis. Therefore,

miR-15 and miR-16 are natural antisense Bcl2 interactors that could be

used for therapy of Bcl2-overexpressing tumors. Furthermore, microRNA

expression profiles can distinguish normal B cells from malignant B

cells in CLL. A unique microRNA signature is associated with

prognostic factors such as mutations in the immunoglobulin heavy-chain

variable-region gene (IgV(H)) or high expression of the 70-kd

zeta-associated protein (ZAP-70+) and disease progression in CLL.

Mutations in miRNA transcripts are frequent, some of them germ-line,

and may have functional importance and may predispose to CLL and to a

spectrum of associated malignancies.

PMID: 16616063 [PubMed - in process]