This SuperSeries is composed of the SubSeries listed below.
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Specimen part, Disease, Disease stage, Subject
View SamplesSmall nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs are non-coding RNAs involved in the maturation of other RNA molecules. Alterations of sno/scaRNA expression may play a role in cancerogenesis. This study elucidates the patterns of sno/scaRNA expression in highly purified cells from 211 chronic lymphocytic leukemia (CLL) patients (Binet stage A) also in comparison with those of different normal B-cell subsets. CLLs display a sno/scaRNAs expression profile similar to normal memory, nave and marginal-zone B-cells, with the exception of a few down-regulated transcripts (SNORA31, -6, -62, and -71C). Our analyses also suggest some heterogeneity in the pattern of sno/scaRNAs expression which is apparently unrelated to the major biological (ZAP-70 and CD38), molecular (IGHV mutation) and cytogenetic markers. Moreover, we found that SNORA70F was significantly down-regulated in poor prognostic subgroups and this phenomenon was associated with the down-regulation of its host gene COBLL1. Finally, we generated an independent model based on SNORA74A and SNORD116-18 expression, which appears to distinguish two different prognostic CLL groups. These data extend the view of sno/scaRNAs deregulation in cancer and may contribute to discover novel biomarkers associated with the disease and potentially useful to predict the clinical outcome of early stage CLL patients.
Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia.
No sample metadata fields
View SamplesHighly homologous B-cell receptors, stereotyped BCR, are expressed in a recurrent fraction of patients with chronic lymphocytic leukemia (CLL). In this study, we investigated the biological and molecular features of leukemic cells from 16 patients utilizing stereotyped subset #4 BCR (IGHV4-34) in a prospective cohort of 462 Binet stage A CLL patients. All subset #4 patients were characterized by the IGHV mutated gene configuration and by the absence of unfavorable cytogenetic lesions, and NOTCH1 and SF3B1 mutations. Gene expression profiling demonstrated a significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC genes in leukemic cells from subset #4 compared to those from the remaining IGHV-mutated patients. Similarly, in the cells from subset #4 cases there was a specific miRNA expression pattern involving the upregulation of miR-497 and miR-29c. Furthermore transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, known to be a validated target of this miRNA. Our data identify a distinct gene and miRNA expression profile of the cells from subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the leukemic cells.
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
No sample metadata fields
View SamplesA SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide dosage effect on gene and microRNA expression
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect.
Specimen part, Disease
View SamplesProspective series of 136 clinical monoclonal B lymphocytosis (cMBL) and 216 chronic lymphocytic leukemia (CLL) Rai 0 patients, were investigated in this study. While the distribution of CD38 and ZAP-70 positivity was similar, IGHV-mutated cases were more frequent among cMBL (P = 0.005). A Cox multivariate analysis on the whole patient cohort showed that cMBL condition was predictive of longer PFS, while CD38 expression and IGHV-unmutated status and CD38 expression correlated significantly with a shorter PFS in cMBL and Rai0-CLL, respectively. Trisomy 12, 11q- and 17p- abnormalities were scanty and of no predictive value in both conditions. Notably, gene and miRNA expression profiling showed no significant differences between cMBL and Rai0-CLL. Furthermore, similar gene and miRNA expression signatures were found in cMBL and Rai0-CLL according to the IGHV gene mutational status: that is, unmutated cases had different signatures from mutated cases, irrespectively of the cMBL or CLL condition. Overall, our study based on a prospective series of patients indicates that no major biological differences exist in cMBL compared to Rai0-CLL, suggesting that this two entities mainly differ for the initial size of the monoclonal cell population which may reflect in the longer time for clonal expansion.
Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
No sample metadata fields
View SamplesB-cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course that reflects its heterogeneous genomic pattern. To better define molecular subtypes of the disease, we performed SNP and gene expression profiling microarray analyses in a panel of early stage (Binet A) patients. A clustering analysis of genomic profiles identified four significant groups mainly driven by del(13)(q14) and trisomy 12. Notably, patients with del(13)(q14) were grouped in two separate clusters based on the presence of a biallelic loss and the extension of the deletion. The shorter monoallelic deleted 13q14 region was found to be 635 kb in length, not encompassing the mir-15a/16-1 locus. Interestingly, the mir-15a and mir-16 expression was found to be significantly down-regulated only in patients with biallelic loss. Furthermore, a multiclass supervised analysis identified a different transcriptional signatures in the two genomic subgroups with del(13)(q14). Finally, an integrative approach identified 93 transcripts, mainly mapped to chromosome 12 and 13q12-q14.3, whose expression was significantly correlated with the DNA copy number. Overall, our data further support the notion that transcription deregulation in B-CLL could be mostly due to a gene dosage effect and underscore the presence of two distinct molecular types of 13q14 deleted patients with potential clinical relevance.
Integrative genomics analyses reveal molecularly distinct subgroups of B-cell chronic lymphocytic leukemia patients with 13q14 deletion.
Sex, Specimen part, Disease
View SamplesMultiple myeloma (MM) is characterized by marked genomic instability. Beyond structural rearrangements, a relevant role in its biology is represented by allelic imbalances leading to significant variations in ploidy status. To better elucidate the genomic complexity of MM, we analyzed a panel of 45 patients using combined FISH and microarray approaches. Using a self-developed procedure to infer exact local copy numbers for each sample, we identified a significant fraction of patients showing marked aneuploidy. A conventional clustering analysis showed that aneuploidy, chromosome 1 alterations, hyperdiploidy and recursive deletions at 1p and chromosomes 13, 14 and 22 were the main aberrations driving samples grouping. Then, we integrated mapping information with gene and microRNAs expression profiles: a multiclass analysis of the identified clusters showed a marked gene-dosage effect, particularly concerning 1q transcripts, also confirmed by correlating gene expression levels and local copy number alterations. A wide dosage effect affected also microRNAs, indicating that structural abnormalities in MM closely reflect in their expression imbalances. Finally, we identified several loci in which genes and microRNAs expression correlated with loss-of-heterozygosity occurrence. Our results provide insights into the composite network linking genome structure and gene/microRNA transcriptional features in MM.
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect.
Specimen part, Disease
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