Cytogenetic and therapeutic characterization of primary plasma cell leukemia: the IFM experience

Avet-Loiseau, Hervé; Roussel, Murielle; Campion, Loı̈c; Leleu, Xavier; Marit, Gérald; Jardel, Henry; Dib, Mamoun; Decaux, Olivier; Lamy, Thierry; Tiab, Mourad; Cony-Makhoul, P; Banos, Anne; Lepeu, G.; Lifermann, François; Macro, Margaret; Kolb, Brigitte; Hulin, Cyrille; Caillot, Denis; Traulle, Catherine; Mathiot, Claire; Royer, Bruno

doi:10.1038/leu.2011.176

Cited by 41 publications

(34 citation statements)

References 8 publications

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“…Herein, we identified the occurrence of IGH@ translocations in 87% of pPCL cases; such an incidence overlaps with those reported by several authors [3][4][5][6]8], confirming the widely accepted notion that IGH@ translocations are almost an ubiquitous event in PCL. However, the frequency of the different types of partner loci still remains controversial and this is probably related to the heterogeneous series investigated or geographical factors, as already suggested by other Authors [8].…”

Section: Discussionsupporting

confidence: 73%

“…4). As regards IGH@ translocations involving MAF gene, we found higher frequency (30.5%) than those reported in previous works, where incidence in pPCL was approximately 10-17% [3,4] if not absent [8], and almost identical to that reported by Chiecchio et al [6]. Finally, we found a 13% incidence of t(4;14), quite similar to an earlier report [3] but different from other studies in which it was found at higher frequency (21-25%) [4,5] or completely absent [6,8].…”

Section: Discussioncontrasting

confidence: 56%

“…PPCL can be distinguished from secondary PCL (sPCL) which represents the leukemic transformation of a previously diagnosed multiple myeloma (MM). As described by of t (11;14) and hypodiploidy have been reported [3][4][5][6][7][8]. MYC rearrangements may also occur in pPCL associated with worse clinical outcome [6,8].…”

Section: Introductionmentioning

confidence: 85%

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Genome‐wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles

et al. 2012

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Primary plasma cell leukemia (pPCL) is a rare, yet aggressive form of de novo plasma cell tumor, distinct from secondary PCL (sPCL) which represents a leukemic transformation of pre-existing multiple myeloma (MM). Herein, we performed a comprehensive molecular analysis of a prospective series of pPCLs by means of FISH, single nucleotide polymorphism (SNP) array and gene expression profiling (GEP). IGH@ translocations were identified in 87% of pPCL cases, with prevalence of t(11;14) (40%) and t(14;16) (30.5%), whereas the most frequent numerical alterations involved 1p (38%), 1q (48%), 6q (29%), 8p (42%), 13q (74%), 14q (71%), 16q (53%), and 17p (35%). We identified a minimal biallelic deletion (1.5 Mb) in 8p21.2 encompassing the PPP2R2A gene, belonging to a family of putative tumor suppressors and found to be significantly down-regulated in deleted cases. Mutations of TP53 were identified in four cases, all but one associated with a monoallelic deletion of the gene, whereas activating mutations of the BRAF oncogene occurred in one case and were absent in N-and K-RAS. To evaluate the influence of allelic imbalances in transcriptional expression we performed an integrated genomic analysis with GEP data, showing a significant dosage effect of genes involved in transcription, translation, methyltransferase activity, apoptosis as well as Wnt and NF-kB signaling pathways. Overall, we provide a compendium of genomic alterations in a prospective series of pPCLs which may contribute to improve our understanding of the pathogenesis of this aggressive form of plasma cell dyscrasia and the mechanisms of tumor progression in MM. Am. J. Hematol. 88:16-23, 2013. V

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Section: Discussionsupporting

confidence: 73%

Section: Discussioncontrasting

confidence: 56%

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Genome‐wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles

et al. 2012

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“…All of these adverse characteristics result in short survival, and no standard effective treatments are currently available for these patients. Several studies have investigated PCL in terms of immunophenotype and molecular cytogenetics (5)(6)(7)(8)(9)(10). In contrast, to date, analyses of other molecular aspects of the disease, such as transcriptomic and microRNA (miRNA) profiling, are almost completely lacking (11).…”

Section: Introductionmentioning

confidence: 99%

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

Lionetti

Musto

Martino

et al. 2013

Clinical Cancer Research

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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 Ã , 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.

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“…pPCL is rare, with only 1%-4% of MM patients presenting as pPCL. [4][5][6][7][8][9][10] In addition, Ͻ 1% of patients presenting with extreme leucocytosis (Ͼ 50 ϫ 10 9 /L) are diagnosed with PCL. 11 Compared with classic MM, pPCL has both a different biologic background as well as distinct clinical and laboratory features.…”

Section: Introductionmentioning

confidence: 99%

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et al. 2012

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Cytogenetic and therapeutic characterization of primary plasma cell leukemia: the IFM experience

Cited by 41 publications

References 8 publications

Genome‐wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles

Genome‐wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles

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

How I treat plasma cell leukemia

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