Biological and Clinical Relevance of miRNA Expression Signatures in Primary Plasma Cell Leukemia

Abstract

Purpose: Primary plasma cell leukemia (pPCL) is a rare and very aggressive form of plasma cell dyscrasia. To date, no information on microRNA (miRNA) expression in pPCL has been reported. This study aimed at investigating the involvement of miRNAs in pPCL and their possible relationship with higher tumor aggressiveness.Experimental design: Global miRNA expression profiles were analyzed in highly purified malignant plasma cells from 18 pPCL untreated patients included in a prospective clinical trial. MiRNA expression patterns were evaluated in comparison with a representative series of multiple myeloma patients, in relation to the most recurrent chromosomal abnormalities (as assessed by fluorescence in situ hybridization and single-nucleotide polymorphism-array analysis), and in association with clinical outcome. MiRNA expression was also integrated with gene expression profiles in pPCL and multiple myeloma samples.Results: We identified a series of deregulated miRNAs in pPCL (42 upregulated and 41 downregulated) in comparison with multiple myeloma. Some of them, on the basis of their reported functions and putative target genes computed by integrative analysis, might have a role in the pathobiology of pPCL. As regards chromosomal aberrations, the expression of some miRNAs mapped to hotspot altered regions was associated with DNA copy number of the corresponding loci. Finally, 4 miRNA (miR-497, miR-106b, miR-181a à , and miR-181b) were identified as having expression levels that correlated with treatment response, and 4 (miR-92a, miR-330-3p, miR-22, and miR-146a) with clinical outcome. Conclusions: Overall, our study provides insights into the possible contribution of miRNAs in the pathogenesis of pPCL and suggests targets for future therapeutic investigations.

Primary Plasma Cell Leukemia in the Era of Novel Agents: A Multicenter Study of the Japanese Society of Myeloma

“…Because we could not add to the results of FISH due to the lack of data, we would need to attempt a reanalysis of OS including the FISH results. Recent studies have shown new prognostic factors, including miRNA and gene expression profiles in pPCL, which correlated with treatment response and survival [29,30,31]. In the future, we need to incorporate these data in the prognostic analysis of pPCL.…”

miR-330-3p controls cell proliferation by targeting early growth response 2 in non-small-cell lung cancer

“…Previous studies have shown that miR-330-3p is up-regulated in the blood of patients with prostate cancer and primary plasma cell leukemia [20,21]. Recent studies have demonstrated that miR-330-3p expression was increased in NSCLC patient tissues, and miR-330-3p was also involved in NSCLC brain metastasis with 53-fold higher expression compared with non-metastasis NSCLC [22,23].…”

226 Identification of circulating microRNA signatures for upper tract urothelial carcinoma detection

“…High expression of miR-22 can explain the lack of response in pemetrexed-treated non-small cell lung cancer (NSCLC) patients. However, in primary plasma cell leukemia, miR-22 is associated with a positive clinical outcome (35). One study suggested that circulating miR-431 can contribute to the detection of colorectal cancer (36).…”