microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival

Abstract

Aberrant expression of microRNAs (miRNAs) has been associated with clinical outcome in patients with chronic lymphocytic leukemia (CLL). To identify a powerful and easily assessable miRNA bio-marker of prognosis and survival, we performed quantitative reverse-transcription polymerase chain reaction (qRT-PCR) profiling in 104 CLL patients with a welldefined chromosome 17p status, and we validated our findings with miRNA microarray data from an independent cohort of 80 patients. We found that miR-15a, miR-21, miR-34a, miR-155, and miR-181b were differentially expressed between CLLs with chromosome 17p deletion and CLLs with normal 17p and normal karyotype, and that miR-181b was downregulated in therapy-refractory cases. miR-21 expression levels were significantly higher in patients with poor prognosis and predicted overall survival (OS), and miR-181b expression levels significantly predicted treatment-free survival. We developed a 21FK score (miR-21 qRT-PCR, fluorescence in situ hybridization, Karyotype) to stratify patients according to OS and found that patients with a low score had a significantly longer OS time. When we evaluated the relative power of the 21FK score with the most used prognostic factors, the score was the most significant in both CLL cohorts. We conclude that the 21FK score represents a useful tool for distinguishing between good-prognosis and poor-prognosis CLL patients. (Blood. 2010;116(6):945-952)

Prognostic Role of microRNA-155 in Various Carcinomas: Results from a Meta-Analysis

“…Patients were of a variety of carcinomas, including breast cancer, pancreatic ductal adenocarcinomas, esophageal cancer, hepatocellular carcinoma, leukemia, colorectal cancer, lung cancer and lymphoma. Of all the 28 studies, 16 studies (n = 2536) with HR data could be included for metaanalysis [7,[13][14][15][16][17][18][33][34][35][36][37][38][39][40][41]. Among them, seven studies (n = 1678) recruited lung cancer patients.…”

“…Our previous meta-analysis has shown that elevated expression of miR-21 was a predictor for worse outcome in a variety of cancers, especially in digestive system cancers and head and neck cancers [44]. In some studies, miR-155 was combined with miR-21 or a panel of miRNAs to predict survival [13,14,17,[34][35][36][37]. It is interesting and useful to reveal whether combination application of miR-155 with miR-21 or others has more powerful predictive value than a single miR-155 for universal cancers.…”

Emerging role of microRNA-21 in cancer

“…IL-4 induces B-cell differentiation and survival of CLL cells, and regulation of miR-21 by IL-4 contributes to evasion of apoptosis of CLL cells (43). A study using an miR-21-based scoring system showed that miR-21 expression levels were significantly higher in CLL patients with chromosome 17 deletion (compared with CLL patients without chromosome 17 deletion), which was associated with poor prognosis (44). Although the investigation of miR-21 in acute leukemia is relatively insufficient, miR-21 is frequently overexpressed in myeloid blasts of patients with nucleophosmin-mutant acute myeloid leukemia and associated with a marked downregulation of PDCD4 protein (45).…”

Contribution of microRNAs to CLL Biology and Their Potential as New Biomarkers

“…Further studies, using different molecular techniques, also confirmed the mentioned correlation (Fulci et al, 2007;Marton et al, 2008;Rossi et al, 2010;Stamatopoulos et al, 2009). They reveled also the implication of miR-150 and miR-181 as prognostic factors.…”