A large fraction of trisomy 12, 17p ⁻ , and 11q ⁻ CLL cases carry unidentified microdeletions of <i>miR-15a/16-1</i>

Abstract

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by chromosomal aberrations including 13q, 11q, and 17p deletions and a trisomy of chromosome 12 (T12). 13q deletions are often associated with 11q and 17p deletions in aggressive cases. Conversely, T12 CLLs show a variable prognosis, and association with 13q deletions is uncommon. The <i>miR-15a/16-1</i> cluster is the functional target of 13q deletions, leading to <i>BCL2</i> overexpression. Chromosomal aberrations in CLL are associated with prognosis, and their identification is carried out by fluorescence in situ hybridization (FISH). Since standard FISH only detects large deletions, we investigated the presence of undetected microdeletions targeting <i>miR-15a/16-1</i> in CLL cases. We found that ∼34% of CLL samples show an unreported loss of the <i>miR-15a/16-1</i> locus regardless of their cytogenetic profile. Interestingly, 15 out of 39 (∼39%) of all CLLs with T12, carry microdeletions of <i>miR-15a/16-1</i>, indicating that, in patients with T12, <i>miR-15a/16-1</i> are mostly inactivated by microdeletions. In addition, ∼40% of CLL cases bearing T12, 17p^-, and 11q^- showed unidentified microdeletions of <i>miR-15a/16-1</i>, suggesting that <i>miR-15a/16-1</i> loss cooperates with such chromosomal alterations in CLL. These data may have clinical relevance for the successful stratification of patients for treatment.