Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial

Němec, Pavel; Zemanová, Zuzana; Kuglík, Petr; Michalova, Kyra; Tajtlová, Jana; Kaisarová, Petra; Oltová, Alexandra; Filková, Hana; Holzerová, Milena; Balcárková, Jana; Jarošová, Marie; Rabasova, Jana; Hruba, Martina; Špıčka, Ivan; Gregora, Evžen; Adam, Zdeněk; Scudla, Vlastimil; Maisnar, Vladimír; Schützová, Miroslava

doi:10.3109/10428194.2011.634042

Cited by 37 publications

(28 citation statements)

References 37 publications

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“…The prevalence of adverse abnormalities (51.9%) in this cohort of MM at diagnosis is similar to that in previously published data [2, 3, 12, 16–18]. The combination of unfavourable conventionally used cytogenetic markers, del(17p13) and t(4;14) [19], with two more recent markers, del(1p32) and 1q21 gain, has enabled us to identify 39.0% more patients carrying chromosome 1 abnormalities.…”

Section: Discussionsupporting

confidence: 91%

Combination of t(4;14), del(17p13), del(1p32) and 1q21 gain FISH probes identifies clonal heterogeneity and enhances the detection of adverse cytogenetic profiles in 233 newly diagnosed multiple myeloma

Smol

Dufour²,

Tricot

et al. 2017

Mol Cytogenet

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BackgroundOur aim was to set the FISH combination of del(17p13), t(4;14), 1q21 gain and del(1p32), four adverse cytogenetic factors rarely evaluated together, and compare our technical thresholds with those defined in the literature.MethodsTwo hundred thirty-three patients with MM at diagnosis were studied using FISH to target 4 unfavorable cytogenetic abnormalities: 17p13 deletion, t(4;14) translocation, 1p32 deletion and 1q21 gain. Technical thresholds were determined for each probe using isolated CD138-expressing PC from patients without MM.ResultsThe FISH analysis identified abnormalities in 79.0% of patients. Del(17p13) was detected in 15.0% of cases, t(4;14) in 11.5%, 1q21 gain in 37.8% and del(1p32) in 8.7%. Adding 1p32/1q21 FISH probes has enabled us to identify adverse cytogenetic profiles in 39.0% of patients without del(17p13) or t(4;14). Clonal heterogeneity was observed in 51.1% of patients as well as an increase in the number of adverse abnormalities when related clones were greater than or equal to 2 (85.1% against 45.6%).ConclusionFISH allowed detecting accumulation of adverse abnormalities and clonal heterogeneity in MM with a combination of 4 probes. The impacts of these two parameters need to be evaluated, and could be included in future cytogenetic classifications.

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Section: Discussionsupporting

confidence: 91%

Combination of t(4;14), del(17p13), del(1p32) and 1q21 gain FISH probes identifies clonal heterogeneity and enhances the detection of adverse cytogenetic profiles in 233 newly diagnosed multiple myeloma

Smol

Dufour²,

Tricot

et al. 2017

Mol Cytogenet

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“…46 Two patients had a complex karyotype at presentation, including one with three high-risk abnormalities (translocation t(4;14), gain of the 1q21 region and deletion 17p) -findings that are associated with unfavorable outcome and shorter median survival -whereas two patients had evidence of trisomies of odd-numbered chromosomes (hyperdiploidy) that are typically associated with better survival. 49,50 This distribution of genetic abnormalities is similar to the reported literature and does not indicate a unique subtype of plasma cell myeloma. 46,49,50 Aside from large numbers of IgG4 þ plasma cells, the histological features of bone marrows and soft tissue debridement specimens did not show any characteristics of IgG4-related disease, such as lymphoplasmacytic inflammation, lymphoid follicles with expanded germinal centers, obliterative phlebitis, or prominent cellular fibrosis, composed of activated fibroblasts, lymphocytes, and plasma cells.…”

Section: Discussionsupporting

confidence: 73%

“…49,50 This distribution of genetic abnormalities is similar to the reported literature and does not indicate a unique subtype of plasma cell myeloma. 46,49,50 Aside from large numbers of IgG4 þ plasma cells, the histological features of bone marrows and soft tissue debridement specimens did not show any characteristics of IgG4-related disease, such as lymphoplasmacytic inflammation, lymphoid follicles with expanded germinal centers, obliterative phlebitis, or prominent cellular fibrosis, composed of activated fibroblasts, lymphocytes, and plasma cells. 10,20,[51][52][53][54][55][56][57][58] Despite sustained high serum levels of IgG4, none of the patients fulfilled diagnostic criteria for IgG4-related systemic disease.…”

Section: Discussionsupporting

confidence: 73%

IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease

et al. 2014

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IgG4-related disease is a newly described systemic fibroinflammatory process, characterized by increase in IgG4-positive plasma cells. Its pathogenesis, including the role of IgG4, remains poorly understood. Plasma cell myeloma is typically associated with a large monoclonal serum spike, which is frequently of IgG isotype. We sought to identify and characterize a subset of IgG4-secreting myeloma, as it may provide a biological model of disease with high serum levels of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma expressed IgG4. Four patients were men and two were women, with a mean age of 64 (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non-metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2 g/dl), and none had definite signs or symptoms of IgG4-related disease. Four myelomas had plasmablastic morphology. Four had kappa and two had lambda light chain expression. Three cases expressed CD56. Two patients had a complex karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to have a high rate of plasmablastic morphology and could be predisposed to necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of IgG4-related disease. These findings suggest that the increased number of IgG4-positive plasma cells is not the primary etiologic agent in IgG4-related disease. Elevated serum levels of IgG4 is not sufficient to produce the typical disease presentation and should not be considered diagnostic of IgG4-related disease.

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“…Interphase fluorescence in situ hybridization analysis (I-FISH) was performed as a part of routine diagnostic procedure on CD138 + BMPCs, as previously described 25 (Online Supplementary Methods).…”

Section: Interphase Fluorescence In Situ Hybridization Analysismentioning

confidence: 99%

Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nclassification. 22 In this study, a new serum miRNAs expression profile, potent enough to distinguish newly diagnosed MM and MGUS patients from healthy controls, was created based on TaqMan Low Density Arrays (TLDA). This profile was validated by quantitative realtime PCR (qPCR) on a larger cohort of newly diagnosed and relapsed MM as well as MGUS patients. Moreover, miRNAs levels were correlated with clinical, biochemical and cytogenetic characteristics and survival data. Methods Patients and healthy donorsPeripheral blood (PB) serum samples from 103 newly diagnosed MM patients, 18 MM patients in relapse, 57 MGUS and 30 healthy donors (HD) from the Faculty Hospital Brno, Czech Republic, were obtained for this study. PB serum samples were collected as follows: centrifugation 3500 rpm/15 min/20°C. Samples were frozen as 0.5 mL aliquots, stored at -80°C and thawed only once. For 70 MM and 36 MGUS samples, BMPCs were obtained for routine interphase fluorescence in situ hybridization analysis (I-FISH), as described previously. 23 Patients' and donors' characteristics are described in Table 1 and in the Online Supplementary Table S1. For 6 newly diagnosed MM patients, BMPCs and exosomal and non-exosomal fraction from PB serum were collected. All patients signed an informed consent form approved by the hospital ethical committee before enrollment into this study. MiRNA extractionTotal RNA enriched for miRNAs was extracted from all serum samples using miRNeasy Kit (Qiagen) modified for circulating miRNAs according to the manufacturer's instructions. MiRNA/RNA quantity was assessed on a NanoDrop ND-1000 Spectrophotometer (Thermo Scientific) as measurement of each sample 2 times with mean SD=0.292 ng/μL. All samples fit into the Nanodrop ND-1000 validated measuring range. Exosomes precipitationExosomes were collected using ExoQuick Exosome Precipitation Solution (System Biosciences). Serum samples were centrifuged for 3500 rpm/10 min/4°C, 250 μL of serum was combined with 63 μL of ExoQuick, incubated for 30 min/4°C and centrifuged for 2 min/13000 rpm. Exosomal and non-exosomal fraction was used for miRNA/RNA extraction, as described above. TaqMan Low Density ArraysMegaplex profiling using human TaqMan Low Density miRNA Arrays A+B, v3.0 (TLDA) (Life Technologies) was performed to evaluate the expression of 667 miRNA (see Online Supplementary Methods). QPCR was performed on the ABI7900HT system; raw data were analyzed using SDS software v.2.3, RQ Manager v1.2.1 (Life Technologies). Candidate miRNA confirmation by qPCR and quantification of miRNAIndividual TaqMan miRNA assays for 6 miRNA (hsa-miR-222-002276, hsa-miR-744-002324, hsa-miR-130a-000454, hsa-miR34a-000426, hsa-let-7e-002406, hsa-let-7d-002283, Life Technologies) were used for qPCR on a 7500 Real-Time PCR System. QPCR and reverse transcription was performed following the manufacturer´s recommendations (see Online Supplementary Methods). Absolute quantification to determine the copy number of each miRNA per 1...

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Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial

Cited by 37 publications

References 37 publications

Combination of t(4;14), del(17p13), del(1p32) and 1q21 gain FISH probes identifies clonal heterogeneity and enhances the detection of adverse cytogenetic profiles in 233 newly diagnosed multiple myeloma

Combination of t(4;14), del(17p13), del(1p32) and 1q21 gain FISH probes identifies clonal heterogeneity and enhances the detection of adverse cytogenetic profiles in 233 newly diagnosed multiple myeloma

IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease

Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance

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