Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group

Braulke, Friederike; Platzbecker, Uwe; Müller‐Thomas, Catharina; Götze, Katharina; Germing, Ulrich; Brümmendorf, Tim H.; Nolte, Florian; Hofmann, Wolf‐Karsten; Giagounidis, Aristoteles; Lübbert, Michael; Greenberg, Peter L.; Bennett, John M.; Solé, Françesc; Mallo, Mar; Slovak, Marilyn L.; Ohyashiki, Kazuma; Beau, Michelle M. Le; Tüchler, Heinz; Pfeilstöcker, Michael; Nösslinger, Thomas; Hildebrandt, Barbara; Shirneshan, Katayoon; Aul, Carlo; Stauder, Reinhard; Sperr, Wolfgang R.; Valent, Peter; Fonatsch, Christa; Trümper, Lorenz; Haase, Detlef; Schanz, Julie

doi:10.3324/haematol.2014.110452

Cited by 19 publications

(14 citation statements)

References 26 publications

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“…The proportion of cells with LOY was determined by FISH analysis using commercially available DNA probes specific for chromosomes X and Y (CEP X SpectrumOrange™/Y SpectrumGreen™, Abbott GmbH & Company, KG, Wiesbaden, Germany). Further commercially available DNA probes were used to screen CD34+ peripheral blood cells of MDS patients for the most frequent cytogenetic aberrations detectable in MDS patients as described before (Braulke et al, , ). A case was considered positive for LOY if this abnormality was observed in at least three metaphases by banding analysis or if the percentage of cells with LOY exceeded our laboratory threshold of 7.5% for LOY in CD34+ peripheral blood cells.…”

Section: Methodsmentioning

confidence: 99%

New data shed light on Y‐loss‐related pathogenesis in myelodysplastic syndromes

Ganster

Kämpfe

Jung

et al. 2015

Genes Chromosomes & Cancer

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Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition.

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Section: Methodsmentioning

confidence: 99%

New data shed light on Y‐loss‐related pathogenesis in myelodysplastic syndromes

Ganster

Kämpfe

Jung

et al. 2015

Genes Chromosomes & Cancer

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“…Use of an extended panel of fluorescent in situ hybridization probes on PB mononuclear cells enriched for CD34+ although helpful but is limited to identifying only predefined lesions. 16 Our previously published pilot study has shown the utility of molecular assays such as targeted gene sequencing and SNP-A karyotyping, using PB as a surrogate for BM. 17 Following on from this preliminary work, we extended the cohort (n = 201) and have optimized a sequencing gene panel targeting the 24 frequently mutated genes in MDS and a high-resolution SNP array for karyotyping to determine whether genetic abnormalities in the BM are reflected in the PB thus enabling easy assessment of response to treatment and/or disease progression.…”

Section: Introductionmentioning

confidence: 99%

High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS)

et al. 2015

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Bone marrow (BM) genetic abnormalities in myelodysplastic syndrome (MDS) have provided important biological and prognostic information; however, frequent BM sampling in older patients has been associated with significant morbidity. Utilizing single-nucleotide polymorphism array (SNP-A) and targeted gene sequencing (TGS) of 24 frequently mutated genes in MDS, we assessed the concordance of genetic abnormalities in BM and peripheral blood (PB) samples concurrently from 201 MDS patients. SNP-A karyotype in BM was abnormal in 108 (54%) and normal in 93 (46%) patients, with 95% (190/201) having an identical PB karyotype. The median copy number (CN) for deletions was significantly lower in BM (CN:1.4 (1-1.9)) than in PB (CN:1.5 (1-1.95), P<0.001). Using TGS, 71% (130/183) patients had BM somatic mutations with 95% (124/130) having identical mutations in PB. The mutant allele burden was lower in PB (median 27% (1-96%)) compared with BM (median 29% (1-100%); P=0.14) with no significant difference in the number, types of mutations or World Health Organization subtype. In all patients with discordant SNP (n=11) and mutation (n=6) profiles between BM and PB, shared abnormalities were always present irrespective of treatment status. Overall, 86% of patients had a clonal aberration with 95% having identical SNP-A karyotype and mutations in PB, thus enabling frequent assessment of response to treatment and disease evolution especially in patients with fibrotic or hypocellular marrows.

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“…Especially relevant for bone marrow samples of MDS patients with fibrotic or hypocellular marrows, where chromosome banding of marrow metaphases often fails and cytogenetic information is missing. Fluorescence in situ hybridization (FISH) with targeted probes can overcome this limitation, as it can identify a subset of cytogenetic abnormalities in patient samples with no or poor morphology metaphases . However, FISH analysis with targeted probe panels is labor intensive and requires the ability to screen a large number of cells.…”

Section: Introductionmentioning

confidence: 99%

Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial

Stevens‐Kroef

Weghuis

ElIdrissi-Zaynoun

et al. 2017

Genes Chromosomes & Cancer

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Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP-based genomic array profiling is a high-resolution tool that also enables genome wide analysis. We compared karyotyping with oligo/SNP-based array profiling in 104 MDS patients from the HOVON-89 study. Oligo/SNP-array identified all cytogenetically defined genomic lesions, except for subclones in two cases and balanced translocations in three cases. Conversely, oligo/SNP-based genomic array profiling had a higher success rate, showing 55 abnormal cases, while an abnormal karyotype was found in only 35 patients. In nine patients whose karyotyping was unsuccessful because of insufficient metaphases or failure, oligo/SNP-based array analysis was successful. Based on cytogenetic visible abnormalities as identified by oligo/SNP-based genomic array prognostic scores based on IPSS/-R were assigned. These prognostic scores were identical to the IPSS/-R scores as obtained with karyotyping in 95%-96% of the patients. In addition to the detection of cytogenetically defined lesions, oligo/SNP-based genomic profiling identified focal copy number abnormalities or regions of copy neutral loss of heterozygosity that were out of the scope of karyotyping and fluorescence in situ hybridization. Of interest, in 26 patients we demonstrated such cytogenetic invisible abnormalities. These abnormalities often involved regions that are recurrently affected in hematological malignancies, and may therefore be of clinical relevance. Our findings indicate that oligo/SNP-based genomic array can be used to identify the vast majority of recurrent cytogenetic abnormalities in MDS. Furthermore, oligo/SNP-based array profiling yields additional genetic abnormalities that may be of clinical importance.

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Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group

Cited by 19 publications

References 26 publications

New data shed light on Y‐loss‐related pathogenesis in myelodysplastic syndromes

New data shed light on Y‐loss‐related pathogenesis in myelodysplastic syndromes

High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS)

Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial

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