12 results on '"Baldus, Claudia D."'
Search Results
2. Dominant T-cell Receptor Delta Rearrangements in B-cell Precursor Acute Lymphoblastic Leukemia: Leukemic Markers or Physiological γδ T Repertoire?
- Author
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Kelm, Miriam, Darzentas, Franziska, Darzentas, Nikos, Kotrova, Michaela, Wessels, Wiebke, Bendig, Sonja, Baldus, Claudia D., Lettau, Marcus, Gökbuget, Nicola, Kabelitz, Dieter, Brüggemann, Monika, and Chitadze, Guranda
- Published
- 2023
- Full Text
- View/download PDF
3. High erythroferrone expression in CD71+ erythroid progenitors predicts superior survival in myelodysplastic syndromes.
- Author
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Riabov, Vladimir, Mossner, Maximilian, Stöhr, Alexandra, Jann, Johann‐Christoph, Streuer, Alexander, Schmitt, Nanni, Knaflic, Antje, Nowak, Verena, Weimer, Nadine, Obländer, Julia, Palme, Iris, Schumann, Christiane, Baldus, Claudia D., Schulze, Torsten J., Wuchter, Patrick, Röhl, Henning, Jawhar, Ahmed, Weiss, Christel, Boch, Tobias, and Metzgeroth, Georgia
- Subjects
MYELODYSPLASTIC syndromes ,IRON metabolism ,GENETIC mutation ,STATISTICAL significance ,DISEASE progression - Abstract
Summary: Ineffective erythropoiesis and iron overload are common in myelodysplastic syndromes (MDS). Erythroferrone (ERFE) and growth/differentiation factor 15 (GDF15) are two regulators of iron homeostasis produced by erythroid progenitors. Elevated systemic levels of ERFE and GDF15 in MDS are associated with dysregulated iron metabolism and iron overload, which is especially pronounced in MDS with SF3B1 gene mutations. However, the role of ERFE and GDF15 in MDS pathogenesis and their influence on disease progression are largely unknown. Here, we analyzed the expression of ERFE and GDF15 in CD71+ erythroid progenitors of n = 111 MDS patients and assessed their effects on patient survival. The expression of ERFE and GDF15 in MDS was highly aberrant. Unexpectedly, ERFE expression in erythroprogenitors was highly relevant for MDS prognosis and independent of International Prognostic Scoring System (IPSS) stratification. Although ERFE expression was increased in patients with SF3B1 mutations, it predicted overall survival (OS) in both the SF3B1wt and SF3B1mut subgroups. Of note, ERFE overexpression predicted superior OS in the IPSS low/Int‐1 subgroup and in patients with normal karyotype. Similar observations were made for GDF15, albeit not reaching statistical significance. In summary, our results revealed a strong association between ERFE expression and MDS outcome, suggesting a possible involvement of ERFE in molecular MDS pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Aneuploidy in children with relapsed B‐cell precursor acute lymphoblastic leukaemia: clinical importance of detecting a hypodiploid origin of relapse.
- Author
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Groeneveld‐Krentz, Stefanie, Schroeder, Michael P., Reiter, Michael, Pogodzinski, Malwine J., Pimentel‐Gutiérrez, Helia J., Vagkopoulou, Renia, Hof, Jana, Chen‐Santel, Christiane, Nebral, Karin, Bradtke, Jutta, Türkmen, Seval, Baldus, Claudia D., Gattenlöhner, Stefan, Haas, Oskar A., Stackelberg, Arend, Karawajew, Leonid, Eckert, Cornelia, and Kirschner‐Schwabe, Renate
- Subjects
ANEUPLOIDY ,CHROMOSOMES ,MULTIVARIATE analysis ,CHILDREN ,ALTERNATIVE medicine - Abstract
Summary: Aneuploidy is common in paediatric B‐cell precursor acute lymphoblastic leukaemia (ALL). Specific subgroups, such as high hyperdiploidy (>50 chromosomes or DNA Index ≥1·16) and hypodiploidy (<45 chromosomes), predict outcome of patients after primary treatment. Whether aneuploidy has a prognostic value for relapsed disease is yet to be determined. Using DNA index and centromere screening by multiplex ligation‐dependent probe amplification, we investigated aneuploidy in 413 children treated for first relapse of B‐cell precursor ALL according to the ALL‐REZ BFM 2002 protocol. Ten‐year event‐free survival of patients with high hyperdiploid relapses approached 70%, whereas it was only 40% in low hyperdiploid relapses. Three patients with apparent hyperdiploid relapse had TP53 mutations. In these cases, array‐based allelotyping revealed a hypodiploid origin with absence of the hypodiploid founder clone (masked hypodiploidy). Collectively, patients with evident or masked hypodiploid relapses showed an extremely low event‐free survival rate of 9%. Importantly, the current relapse risk stratification did not identify cases with masked hypodiploidy as high‐risk patients, due to their favourable clinical presentation. In multivariate analysis, hypodiploidy proved to be an independent prognostic factor. This finding supports stratification of relapses with hypodiploid origin into high‐risk arms in future trials or allocation of patients to alternative treatment approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
5. IGH Rearrangement Evolution in Adult KMT2A -rearranged B-cell Precursor ALL: Implications for Cell-of-origin and MRD Monitoring.
- Author
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Darzentas, Franziska, Szczepanowski, Monika, Kotrová, Michaela, Kelm, Miriam, Hartmann, Alina, Beder, Thomas, Gökbuget, Nicola, Neumann, Martin, Bastian, Lorenz, Baldus, Claudia D., Pál, Karol, Darzentas, Nikos, and Brüggemann, Monika
- Published
- 2023
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6. A novel approach to detect resistance mechanisms reveals FGR as a factor mediating HDAC inhibitor SAHA resistance in B-cell lymphoma.
- Author
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Joosten, Maria, Ginzel, Sebastian, Blex, Christian, Schmidt, Dmitri, Gombert, Michael, Chen, Cai, Linka, René Martin, Gräbner, Olivia, Hain, Anika, Hirsch, Burkhard, Sommerfeld, Anke, Seegebarth, Anke, Gruber, Uschi, Maneck, Corinna, Zhang, Langhui, Stenin, Katharina, Dieks, Henrik, Sefkow, Michael, Münk, Carsten, and Baldus, Claudia D.
- Abstract
Histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) are not commonly used in clinical practice for treatment of B-cell lymphomas, although a subset of patients with refractory or relapsed B-cell lymphoma achieved partial or complete remissions. Therefore, the purpose of this study was to identify molecular features that predict the response of B-cell lymphomas to SAHA treatment. We designed an integrative approach combining drug efficacy testing with exome and captured target analysis (DETECT). In this study, we tested SAHA sensitivity in 26 B-cell lymphoma cell lines and determined SAHA-interacting proteins in SAHA resistant and sensitive cell lines employing a SAHA capture compound (CC) and mass spectrometry (CCMS). In addition, we performed exome mutation analysis. Candidate validation was done by expression analysis and knock-out experiments. An integrated network analysis revealed that the Src tyrosine kinase Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog (FGR) is associated with SAHA resistance. FGR was specifically captured by the SAHA-CC in resistant cells. In line with this observation, we found that FGR expression was significantly higher in SAHA resistant cell lines. As functional proof, CRISPR/Cas9 mediated FGR knock-out in resistant cells increased SAHA sensitivity. In silico analysis of B-cell lymphoma samples (n = 1200) showed a wide range of FGR expression indicating that FGR expression might help to stratify patients, which clinically benefit from SAHA therapy. In conclusion, our comprehensive analysis of SAHA-interacting proteins highlights FGR as a factor involved in SAHA resistance in B-cell lymphoma. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
7. Close correlation of copy number aberrations detected by next-generation sequencing with results from routine cytogenetics in acute myeloid leukemia.
- Author
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Vosberg, Sebastian, Herold, Tobias, Hartmann, Luise, Neumann, Martin, Opatz, Sabrina, Metzeler, Klaus H., Schneider, Stephanie, Graf, Alexander, Krebs, Stefan, Blum, Helmut, Baldus, Claudia D., Hiddemann, Wolfgang, Spiekermann, Karsten, Bohlander, Stefan K., Mansmann, Ulrich, and Greif, Philipp A.
- Published
- 2016
- Full Text
- View/download PDF
8. TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation.
- Author
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Middeke, Jan M., Herold, Sylvia, Rücker‐Braun, Elke, Berdel, Wolfgang E., Stelljes, Matthias, Kaufmann, Martin, Schäfer‐Eckart, Kerstin, Baldus, Claudia D., Stuhlmann, Reingard, Ho, Anthony D., Einsele, Hermann, Rösler, Wolf, Serve, Hubert, Hänel, Mathias, Sohlbach, Kristina, Klesse, Christian, Mohr, Brigitte, Heidenreich, Falk, Stölzel, Friedrich, and Röllig, Christoph
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ACUTE myeloid leukemia ,HEMATOPOIETIC stem cells ,CYTOGENETICS ,PROGNOSIS ,GENETIC mutation ,PATIENTS - Abstract
Treatment success in patients with acute myeloid leukaemia ( AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation ( HSCT). Samples of 97 patients with AML and adverse-risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67 months, the three-year probabilities of overall survival ( OS) and event-free survival for patients with TP53 wild type were 33% [95% confidence interval ( CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) ( P = 0·002 and P = 0·007) for those with mutated TP53, respectively. In multivariate analysis, the TP53-mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
9. R-split- CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma.
- Author
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Kreher, Stephan, Lammer, Felicitas, Augustin, Dieter, Pezzutto, Antonio, and Baldus, Claudia D.
- Subjects
IMMUNOTHERAPY ,CYCLOPHOSPHAMIDE ,DOXORUBICIN ,RITUXIMAB ,CANCER chemotherapy ,B cell lymphoma - Abstract
Objectives Chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R- CHOP) is the standard of care for patients with diffuse large B-cell lymphoma ( DLBCL). However, management of elderly patients is challenging as critical comorbidities often account for increased number of treatment-related complications. Patients and methods In the past 8 yrs, we have treated elderly patients with a full-dose R- CHOP regimen by splitting the administration of cyclophosphamide and doxorubicin over 2 days (R-split- CHOP) to reduce peak plasma level. Here, we retrospectively analyzed the results of 30 patients with newly diagnosed DLBCL. Results The overall response rate was found to be 87%, the overall survival probability after 3 yrs was 60.6% (95% CI, 42.1%-79.0%), and the progression-free survival probability was 49.7% (95% CI, 30.4%-68.9%). Grade 3/4 infectious complications were reported in 30% of patients, yet no treatment-related deaths occurred. Conclusion We suggest that R-split- CHOP could be a valuable option to safely administer full-dose-intensity R- CHOP to elderly patients at risk of treatment-related complications. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
10. Expression of IGFBP7 in acute leukemia is regulated by DNA methylation.
- Author
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Heesch, Sandra, Bartram, Isabelle, Neumann, Martin, Reins, Jana, Mossner, Maximilian, Schlee, Cornelia, Stroux, Andrea, Haferlach, Torsten, Goekbuget, Nicola, Hoelzer, Dieter, Hofmann, Wolf-Karsten, Thiel, Eckhard, and Baldus, Claudia D.
- Abstract
The important role of insulin-like growth factor binding protein 7 ( IGFBP7) as a tumor suppressor in solid tumors has been revealed in several studies. Interestingly, in a recent study IGFBP7 was also shown to be aberrantly expressed in acute leukemia. Moreover, in acute T-lymphoblastic leukemia (T-ALL), high IGFBP7 expression predicts primary therapy resistance. In order to elucidate the mechanisms underlying aberrant IGFBP7 expression, we used pyrosequencing technology to investigate the DNA methylation of IGFBP7 in 109 T-ALL patient samples. Aberrant methylation was shown and hypomethylation was associated with an early immunophenotype and co-expression of the stem cell markers CD117 ( P < 0.001) and CD34 ( P < 0.001). In concordance, gene expression profiles of 86 T-ALL patients revealed upregulation of stem cell markers ( CD34 and CD133) as well as genes associated with poor outcome and pathogenesis of leukemia ( MN1, BAALC, FLT3) in the high IGFBP7 expression group. In conclusion, aberrant IGFBP7 expression is regulated by DNA methylation in acute leukemia. Hypomethylation of the gene is likely to characterize an immature and a more malignant subtype of the disease. ( Cancer Sci 2011; 102: 253-259) [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
11. Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review.
- Author
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Baldus, Claudia D., Mrózek, Krzysztof, Marcucci, Guido, and Bloomfield, Clara D.
- Subjects
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MYELOID leukemia , *CYTOGENETICS , *MOLECULAR genetics , *PROGNOSIS , *KARYOTYPES , *GENE expression , *PATIENTS - Abstract
Normal cytogenetics are detected pretreatment in approximately 45% of patients with de novo acute myeloid leukaemia (AML); thus this constitutes the single largest cytogenetic group of AML. Recently, molecular genetic alterations with prognostic significance have been reported in these patients. They include internal tandem duplication of the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA and NPM1 genes and aberrant expression of the BAALC, ERG and MN1 genes. Additionally, gene-expression profiling has been applied to identify prognostically relevant subgroups. Substantial progress has been made in the understanding of molecular pathways deregulated in leukaemogenesis and how these defects can be targeted by novel therapeutic compounds. Here we critically review the molecular heterogeneity among AML patients with normal cytogenetics and discuss how these data may translate into a prognostic, molecular-based treatment stratification that may improve the currently unsatisfactory outcome of these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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- View/download PDF
12. High erythroferrone expression in CD71 + erythroid progenitors predicts superior survival in myelodysplastic syndromes.
- Author
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Riabov V, Mossner M, Stöhr A, Jann JC, Streuer A, Schmitt N, Knaflic A, Nowak V, Weimer N, Obländer J, Palme I, Schumann C, Baldus CD, Schulze TJ, Wuchter P, Röhl H, Jawhar A, Weiss C, Boch T, Metzgeroth G, Neumann M, Hofmann WK, Nolte F, and Nowak D
- Subjects
- Adult, Aged, Aged, 80 and over, Erythroid Precursor Cells chemistry, Female, Growth Differentiation Factor 15 biosynthesis, Growth Differentiation Factor 15 genetics, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Peptide Hormones genetics, Phosphoproteins genetics, Proportional Hazards Models, RNA Splicing Factors genetics, Treatment Outcome, Young Adult, Antigens, CD analysis, Erythroid Precursor Cells metabolism, Myelodysplastic Syndromes metabolism, Peptide Hormones biosynthesis, Receptors, Transferrin analysis
- Abstract
Ineffective erythropoiesis and iron overload are common in myelodysplastic syndromes (MDS). Erythroferrone (ERFE) and growth/differentiation factor 15 (GDF15) are two regulators of iron homeostasis produced by erythroid progenitors. Elevated systemic levels of ERFE and GDF15 in MDS are associated with dysregulated iron metabolism and iron overload, which is especially pronounced in MDS with SF3B1 gene mutations. However, the role of ERFE and GDF15 in MDS pathogenesis and their influence on disease progression are largely unknown. Here, we analyzed the expression of ERFE and GDF15 in CD71
+ erythroid progenitors of n = 111 MDS patients and assessed their effects on patient survival. The expression of ERFE and GDF15 in MDS was highly aberrant. Unexpectedly, ERFE expression in erythroprogenitors was highly relevant for MDS prognosis and independent of International Prognostic Scoring System (IPSS) stratification. Although ERFE expression was increased in patients with SF3B1 mutations, it predicted overall survival (OS) in both the SF3B1wt and SF3B1mut subgroups. Of note, ERFE overexpression predicted superior OS in the IPSS low/Int-1 subgroup and in patients with normal karyotype. Similar observations were made for GDF15, albeit not reaching statistical significance. In summary, our results revealed a strong association between ERFE expression and MDS outcome, suggesting a possible involvement of ERFE in molecular MDS pathogenesis., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2021
- Full Text
- View/download PDF
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