Upregulation of translational machinery and distinct genetic subgroups characterise hyperdiploidy in multiple myeloma

Agnelli, Luca; Fabris, Sonia; Bicciato, Silvio; Basso, Dario; Baldini, Luca; Morabito, Fortunato; Verdelli, Donata; Todoerti, Katia; Lambertenghi-Deliliers, Giorgio; Lombardi, Luigia; Neri, Antonino

doi:10.1111/j.1365-2141.2006.06467.x

Cited by 64 publications

(78 citation statements)

References 33 publications

(66 reference statements)

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“…These results are similar to the previously reported frequencies of H-MM and NH-MM. [33][34][35] It is notable that the classification is capable of discerning H-MM by virtue of wholechromosome gains but cannot readily identify differences in the incidence of IgH translocations.…”

Section: Comparisons Of Somatic Copy Number Changes Between Aa and Eamentioning

confidence: 99%

Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach

Baker

Braggio

Jacobus

et al. 2013

Blood

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Epidemiological data have suggested that African American (AA) persons are twice as likely to be diagnosed with multiple myeloma (MM) compared with European American (EA) persons. Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from 3 studies and 353 EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs 52%; P 5 .032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based on gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients. ECOG E4A03 is registered with ClinicalTrials.gov, number NCT00098475. ECOG E9487 is a companion validation set to the ECOG study E9486 and is registered with

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Section: Comparisons Of Somatic Copy Number Changes Between Aa and Eamentioning

confidence: 99%

Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach

Baker

Braggio

Jacobus

et al. 2013

Blood

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“…The supervised gene expression analyses were performed using the significance analysis of microarrays software (SAM version 4.0; Excel front-end publicly available at http:// www-stat.stanford.edu//tibs/SAM/index.html; ref. 32) as previously reported (33). The stringency level of the 90th percentile of false discovery rate being equal to zero was applied.…”

Section: Gene Expression Profilingmentioning

confidence: 99%

Clinical Monoclonal B Lymphocytosis versus Rai 0 Chronic Lymphocytic Leukemia: A Comparison of Cellular, Cytogenetic, Molecular, and Clinical Features

Morabito

Mosca

Cutrona

et al. 2013

Clinical Cancer Research

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Purpose: To investigate the incidence and clinical relevance of classic and new prognostic markers, IGHV gene mutational status, and chromosomal abnormalities in clinical monoclonal B lymphocytosis (cMBL) compared with Rai stage 0 chronic lymphocytic leukemia (Rai0-CLL).Experimental Design: A group of 136 patients with cMBL and a group of 216 Rai0-CLL cases were investigated prospectively.Results: IGHV-mutated cases were significantly more frequent among cMBLs (P ¼ 0.005), whereas the distribution of CD38 and ZAP-70 positive cases, of patients with NOTCH1 and SF3B1 mutations or exhibiting the major CLL cytogenetic abnormalities, was similar in the two groups. Moreover, no significant differences were found either in IGHV/IGHD/IGHJ gene usage or in the overall prevalence of stereotyped IGHV gene sequences. Cells from cMBL and Rai0-CLL exhibited similar gene and microRNA (miRNA) signatures; in addition, when grouped according to the IGHV mutational status, IGHVunmutated cases showed different transcriptional signatures compared with IGHV-mutated patients, irrespective of the cMBL or Rai0-CLL classification. cMBL diagnosis per se was predictive of longer progression-free survival.Conclusions: Our study based on a prospective series of patients indicates that no major differences exist between the circulating cells from cMBL and Rai0-CLL, at least based on a comparison of the markers used in the study. This possibly suggests that the two conditions mainly differ in the initial size of the monoclonal cell population, which may influence the subsequent timing of clonal expansion and clinical manifestations.

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“…The differentially expressed genes discriminating the considered classes were identified using the Significant Analysis of Microarrays software version 4.00 as previously described (19). The functional annotation analysis on the selected lists was carried out using the gene set enrichment analysis (GSEA; ref.…”

Section: Microarray Data Analysismentioning

confidence: 99%

Transcriptional Characterization of a Prospective Series of Primary Plasma Cell Leukemia Revealed Signatures Associated with Tumor Progression and Poorer Outcome

Todoerti

Agnelli

Fabris

et al. 2013

Clinical Cancer Research

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Purpose: Plasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia that presents either as a progression of previously diagnosed multiple myeloma, namely secondary PCL, or as initial manifestation of disease, namely primary PCL (pPCL). Although the presenting signs and symptoms include those seen in multiple myeloma, pPCL is characterized by several aspects that define a more aggressive course. Here, we have investigated the transcriptome of pPCLs and correlated differential expression profiles with outcome to provide insights into the biology of the disease. Experimental Design: The expression profiles of 21 newly diagnosed pPCLs included in a multicenter prospective clinical trial were generated using high-density microarray, then evaluated in comparison with a representative series of patients with multiple myeloma and in association with clinical outcome. Results: All but one of the pPCLs had one of the main immunoglobulin heavy-chain locus translocations, whose associated transcriptional signatures resembled those observed in multiple myeloma. A 503-gene signature distinguished pPCL from multiple myeloma, from which emerged 26 genes whose expression trend was associated with progressive stages of plasma cells dyscrasia in a large dataset from multiple institutions, including samples from normal donors throughout PCL. Finally, 3 genes were identified as having expression levels that correlated with response to the first-line treatment with lenalidomide/dexamethasone, whereas a 27-gene signature was associated with overall survival independently of molecular alterations, hematologic parameters, and renal function. Conclusions: Overall, our data contribute to a fine dissection of pPCL and may provide novel insights into the molecular definition of patients with poorer prognosis. Clin Cancer Res; 19(12); 3247–58. ©2013 AACR.

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Upregulation of translational machinery and distinct genetic subgroups characterise hyperdiploidy in multiple myeloma

Cited by 64 publications

References 33 publications

Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach

Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach

Clinical Monoclonal B Lymphocytosis versus Rai 0 Chronic Lymphocytic Leukemia: A Comparison of Cellular, Cytogenetic, Molecular, and Clinical Features

Transcriptional Characterization of a Prospective Series of Primary Plasma Cell Leukemia Revealed Signatures Associated with Tumor Progression and Poorer Outcome

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