MicroRNA profiling of human chronic lymphocytic leukemia samples to identify whether microRNA profiles are prognostic indicators
ABSTRACT: MicroRNA expression profiles can distinguish normal B cells from malignant B cells in chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. We evaluated the microRNA expression profiles of 94 samples of CLL cells for which ZAP-70 expression, mutations in the rearranged IgVH gene, and the time from diagnosis to initial treatment were known. We also investigated the presence of abnormalities in the genomic sequence of 42 microRNA genes.
SUBMITTER: Claudia Roldo Carlo M. CroceRamiro GarzonMasayoshi ShimizuGeorge CalinMuller FabbriRodolfo IulianoManuela FerracinAmelia CimminoMassimo NegriniHansjuerg AlderGeorge A. CalinGianpiero Di LevaSylwia WojcikRosa VisoneMarilena V. IorioFlavia PichiorriThomas J. KippsCinzia SevignaniStefano VoliniaChang-gong LiuLaura RassentiTiziana PalumboNuretin I. Sever
BACKGROUND: MicroRNA expression profiles can be used to distinguish normal B cells from malignant B cells in patients with chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. METHODS: We evaluated the microRNA expression profiles of 94 samples of CLL cells for which the level of expression of 70-kD zeta-associated protein (ZAP-70), the mutational status of the rearranged immunoglobulin heavy-chain variable-region (IgV ...[more]
Project description:MicroRNA expression profiles can distinguish normal B cells from malignant B cells in chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. We evaluated the microRNa expression profiles of 94 samples of CLL cells for which ZAP-70 expression; mutations in the rearranged IgVH gene; and the time from diagnosis to initial treatment were known. We also investigated the presence of abnormalities in the genomic sequence of 42 microRNA genes.
Project description:We studied the value of the microRNAs as a signature for CLL patients with specific chromosomal abnormalities. We identified 32 microRNAs able to discriminate the 11q deletion, 17p deletion, trisomy 12, and 13q deletion and normal karyotype cytogenetic subgroups. The expression values of 9 among the 32 microRNAs (miR-151-3p, miR-34a, miR-29c, miR-29b, miR-155, miR-148a, miR-146a, miR-146b5p and miR-640) were correlated with genes expression data from the same samples to assess their biological impact on CLL. In this study we also found that IGHV unmutated, high expression of ZAP-70 protein and low expression of the miR-223, miR-29c, miR-29b, and miR-181 family were strongly associated with disease progression in CLL cases harboring 17p deletion; whereas in those harboring trisomy 12 only high expression of the miR-181a, among the analyzed parameters, suggested more aggressive disease. Thus, the use of the microRNA-based classifications may yield clinically useful bio-markers of tumor behavior in CLL.
Project description:MicroRNA expression profiles in response to LBH589 were examined in order to identify HDACi-induced alterations in miRNA expression that regulate apoptotic signaling in chronic lymphocytic leukemia.plasia. miRNA microarray analysis identified unique alterations in miRNA profile that could be used to identify new pathways for apoptosis regulation in CLL.
Project description:We studied the value of the microRNAs as a signature for Chronic lymphocytic leukemia (CLL) patients with specific chromosomal abnormalities. We found that MiR-181b is abiomarker of disease progression in Chronic Lymphocytic Leukemia
Project description:microRNA expression microarray data for analysis of BAALC- and ERG-related miR-expression signatures in older patients with cytogenetically normal AML. The signal intensity was calculated for each spot making an adjustment for local background (i.e., mean foreground minus the median background). Signal intensities less than one were set equal to one and then log-transformed. Log-intensities from replicate spots were averaged. Quantile normalization was performed on arrays using all human and mouse microRNA probes represented on the array. For each microRNA probe, an adjustment was made for batch effects (ie, differences in expression related to the batch in which arrays were hybridized). The normalized data has not been submitted to ArrayExpress.
Project description:A critical question in molecular oncology is how extensive is the involvement of non-codingRNAs (ncRNAs) in human tumorigenesis. Herein, we report that a large fraction of genomic ultraconserved regions (UCRs) are encoding a particular set of ncRNAs and are altered in human cancers. We show that UCRs are frequently located at fragile sites and genomic regions involved in cancers, and that genome-wide UCRs profiling reveals distinct signatures in human leukemias and carcinomas. We proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells, and we identified UCRs whose expression may be regulated by miRNAs abnormally expressed in human chronic lymphocytic leukemia (CLL). Our findings argue that non-coding genes are involved in tumorigenesis at a greater extent as thought before and offer the perspective of identification of signatures associated with diagnosis, prognosis and response to treatment composed by various categories of ncRNA genes.
Project description:MicroRNAs are a class of small non-coding RNAs that control gene expression by targeting messenger RNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, microRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where microRNA signatures were associated with specific clinico-biological features. Here, we show that, in comparison to normal breast tissue, microRNAs are also aberrantly expressed in human breast cancer. The overall microRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated microRNAs being mir-125b, mir-145, mir-21, mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify microRNAs whose expression was correlated with specific breast cancer bio-pathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion or proliferation index.