Downregulation of miR-15a and miR-16-1 at 13q14 in Chronic Lymphocytic Leukemia
摘要
Featured Article: Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2002;99:15524–9.2 MicroRNAs (miRNAs)3 are involved in many biological processes due to their posttranscriptional gene regulation function. Consequently, their crucial role in many diseases, including cancer, is now well known. Nevertheless, the connection between miRNA deregulation and tumorigenesis was unclear for quite some time. In the 2002 article discussed here (1), Dr. Croce's group reported the very first direct association between miRNAs and cancer. In the time preceding this important discovery, Dr. Croce devoted himself to the study of the most common human leukemia: chronic lymphocytic leukemia (CLL). CLL is a malignancy of CD5-positive B cells occurring, for the most part, in individuals over the age of 60 years. At presentation the disease is usually indolent, although it often progresses to an aggressive form. An aggressive form at presentation occurs in 30% of patients. Consistent chromosomal alterations also occur in CLL, with the most common being a deletion of chromosome 13q14, which is observed by cytogenetics in approximately 50% of CLL patients (2). Dr. Croce's group focused its efforts on this region and used a genetic approach called loss of heterozygosity (LOH) to narrow the region of loss and identify the altered gene(s) involved in CLL. After narrowing to approximately 700 kb, the Croce group sequenced this region including the epicenter of loss in the middle. Unfortunately, 7 years of searching amounted to no results. Finally, Dr. Croce decided to consider translocations at 13q14 occurring in CLL, asking colleagues at the CLL Research Consortium for cases of CLLs with such translocations. An interesting opportunity came when Michael Keating of MD Anderson provided Dr. Croce's laboratory with samples of a CLL patient wit