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MicroRNAs in chronic lymphocytic leukemia: from causality to associations and back Expert Rev. Hematol. 5(6), 579–581 (2012)
“MicroRNAs not only arouse interest among researchers
Marek Mraz Author for correspondence: Central European Institute of Technology, Center of Molecular Medicine, Masaryk University, Brno, Czech Republic and Rebecca and John Moores Cancer Center, University of California San Diego, La Jolla, CA, USA Tel.: +1 858 534 9144
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Sarka Pospisilova Author for correspondence: Central European Institute of Technology, Center of Molecular Medicine, Masaryk University, Kamenice 5, Brno, Czech Republic Tel.: +42 077 792 6661 Fax: +42 053 223 4623 sarka.pospisilova@ceitec. muni.cz
studying malignant B-cell physiology but also they theoretically represent therapeutic targets.” Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in the Western world and remains an ‘enigma’ of modern hematology. Notwithstanding intensive research, it is largely unclear what aberrations are associated with the disease onset and its strikingly heterogeneous clinical course. While some patients require treatment immediately after diagnosis, others have an indolent disease that might never require therapy. Interestingly, there is no unifying gene mutation, chromosomal aberration or translocation present in CLL. The most frequent aberration is a deletion of the 13q14 region present in >50% of CLL cases and in other B-cell malignancies including mantle cell lymphoma and multiple myeloma. Researchers were unsuccessfully trying to identify the tumor suppressor(s) located in this region for two decades. The work of Croce and Calin published in 2002 enlightened the field and detailed the first evidence of miRNAs involvement in cancer by indicating that the 13q14 region contains two miRNA genes (miR-15a-16-1) [1] . These miRNAs were shown to target one of the anti-apoptotic molecules (Bcl-2) that supports the survival of malignant B cells, which fits well with the scenario of CLL pathogenesis and progression. A subsequent publication not only implicated the potential use of miRNAs as prognostic markers in CLL but also described inherited germline mutations in miR-16-1 in two CLL cases [2] . Finally, the causality and direct
effect of miR-15a-16-1 was documented in a recent publication reporting a CLL-like phenotype in mice with deletion of these two miRNAs [3] . These studies show a remarkable consistency in data supporting the contribution of miR-16 aberrations to CLL pathogenesis. Surprisingly, large-scale sequencing analysis in >150 CLL cases revealed that mutations in miR-16-1 or other miRNAs are extremely rare in CLL (
