- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Chronic Myeloid Leukemia Treatments
- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Hematopoietic Stem Cell Transplantation
- Hematological disorders and diagnostics
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Treatments and Mutations
- Biosimilars and Bioanalytical Methods
- Cancer-related gene regulation
- Monoclonal and Polyclonal Antibodies Research
- Neutropenia and Cancer Infections
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Genetic factors in colorectal cancer
- Retinoids in leukemia and cellular processes
- MicroRNA in disease regulation
- RNA Research and Splicing
University Hospital Leipzig
2021-2025
Leipzig University
2021-2025
German Cancer Research Center
2015-2024
Heidelberg University
2015-2024
Krankenhaus Barmherzige Brüder
2024
Deutschen Konsortium für Translationale Krebsforschung
2014-2024
Klinik und Poliklinik für Neurologie
2021-2024
LMU Klinikum
2013-2023
Ludwig-Maximilians-Universität München
2014-2023
Munich Leukemia Laboratory (Germany)
2012-2023
Purpose To analyze the frequency and associations with prognostic markers outcome of mutations in IDH genes encoding isocitrate dehydrogenases adult de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients Methods Diagnostic bone marrow or blood samples from 358 patients were analyzed for IDH1 IDH2 by DNA polymerase chain reaction amplification/sequencing. FLT3, NPM1, CEBPA, WT1, MLL mutational analyses gene- microRNA-expression profiling performed centrally. Results found...
To evaluate the prognostic significance of international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML).We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, cytogenetically normal patients, mutational status NPM1, CEBPA, FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), overall (OS) among patients classified into...
Purpose To determine the frequency of TET2 mutations, their associations with clinical and molecular characteristics outcome, associated gene- microRNA-expression signatures in patients primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients Methods Four-hundred twenty-seven CN-AML were analyzed for mutations by polymerase chain reaction direct sequencing established prognostic gene mutations. Gene- profiles derived using microarrays. Results found 23% patients, older age (P...
CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of mutation is prognostic relevance in cytogenetically normal (CN) acute myeloid leukemia (AML).Four hundred sixty-seven homogeneously treated patients with CN-AML were subdivided into moCEBPA, biCEBPA, and wild-type (wt) patients. The subgroups analyzed for clinical parameters additional NPM1, FLT3, MLL genes. Furthermore, we obtained gene expression profiles using...
Targeted immunotherapy in acute myeloid leukemia (AML) is challenged by the lack of AML-specific target antigens and clonal heterogeneity, leading to unwanted on-target off-leukemia toxicity risk relapse from minor clones. We hypothesize that combinatorial targeting AML cells can enhance therapeutic efficacy without increasing toxicity. To identify antigen combinations specific for leukemic stem cells, we generated a detailed protein expression profile based on flow cytometry primary (n =...
Purpose To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics outcome, associated gene- microRNA-expression signatures in primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients Methods Four hundred fifteen previously untreated adults were analyzed for mutations established prognostic gene expression markers. Gene- profiles derived using microarrays. Results Younger (< 60 years; n = 181) older (≥ 234) patients had...
Purpose To determine the association of RUNX1 mutations with therapeutic outcome in younger and older patients primary cytogenetically normal acute myeloid leukemia (CN-AML) gene/microRNA expression signatures. Patients Methods Younger (< 60 years; n = 175) (≥ 225) CN-AML treated intensive cytarabine/anthracycline-based first-line therapy on Cancer Leukemia Group B protocols were centrally analyzed for by polymerase chain reaction direct sequencing established prognostic gene mutations....
Abstract The revised 2017 European LeukemiaNet (ELN) recommendations for genetic risk stratification of acute myeloid leukemia have been widely adopted, but not yet validated in large cohorts AML patients. We studied 1116 newly diagnosed patients (age range, 18–86 years) who had received induction chemotherapy. Among 771 selected by genetics, the ELN-2017 classification re-assigned 26.5% into a more favorable or, commonly, adverse-risk group compared with ELN-2010 recommendations. Forty...
Abstract The revised 2022 European LeukemiaNet (ELN) AML risk stratification system requires validation in large, homogeneously treated cohorts. We studied 1118 newly diagnosed patients (median age, 58 years; range, 18–86 years) who received cytarabine-based induction chemotherapy between 1999 and 2012 compared ELN-2022 to the previous ELN-2017 classification. Key findings were validated a cohort of 1160 mostly younger patients. reclassified 15% patients, 3% into more favorable, 12% adverse...
B-cell maturation antigen (BCMA)-targeting chimeric receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, data on cellular cell dynamics and association with response, resistance or occurrence cytokine release syndrome (CRS) are limited. Therefore, we performed a comprehensive flow cytometry analysis 27 RRMM patients treated Idecabtagene vicleucel (Ide-cel) to assess expansion capacity, persistence effects bystander BCMA-targeting CAR...
Purpose To evaluate the prognostic significance of expression levels a single microRNA, miR-181a, in context established molecular markers cytogenetically normal acute myeloid leukemia (CN-AML), and to gain insight into leukemogenic role miR-181a. Patients Methods miR-181a was measured pretreatment marrow using Ohio State University Comprehensive Cancer Center version 3.0 arrays 187 younger (< 60 years) adults with CN-AML. Presence other prognosticators assessed centrally. A...
To evaluate the impact of miR-155 on outcome adults with cytogenetically normal (CN) acute myeloid leukemia (AML) in context other clinical and molecular prognosticators to gain insight into leukemogenic role this microRNA.We evaluated 363 patients primary CN-AML. levels were measured pretreatment marrow blood by NanoString nCounter assays that quantified expression encoding gene MIR155HG. All assessed centrally. miR-155-associated microRNA profiles derived using microarrays.Considering all...
Philadelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children younger adults. The purpose of this study was a clinical characterization Ph-like ALL Twenty-six (13%) 207 adult patients (median age: 42 years) with (BCP-ALL) were classified as having using gene expression profiling. frequency 27% among 95 BCP-ALL negative for BCR-ABL1 KMT2A-rearrangements. IGH-CRLF2 rearrangements (6/16; P=0.002)...
Molecular risk stratification of acute myeloid leukemia (AML) is largely based on genetic markers. However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance integrating methylation information in AML.Next-generation sequencing analysis methylated identified differentially regions (DMRs) associated with mutations older (≥ 60 years) cytogenetically normal (CN) patients AML (n = 134). Genes...
Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance these clones for AML relapse. Here, we characterized paired pre-treatment and samples from 126 mutations 68 genes. Fifty (40%) retained ≥1 mutation during at VAF ≥2%. Mutation persistence was most frequent DNMT3A (65% diagnosis),...