A5009753849- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA modifications and cancer
- Hematopoietic Stem Cell Transplantation
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- Multiple Myeloma Research and Treatments
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Acute Lymphoblastic Leukemia research
- Histone Deacetylase Inhibitors Research
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Immune cells in cancer
- T-cell and B-cell Immunology
- Cancer-related molecular mechanisms research
- CAR-T cell therapy research
- Renal and related cancers
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Retinoids in leukemia and cellular processes
Heidelberg University
2017-2025
European Molecular Biology Laboratory
2018-2025
University Hospital Heidelberg
2017-2025
German Cancer Research Center
2022
Deutschen Konsortium für Translationale Krebsforschung
2022
Institute for Research in Immunology and Cancer
2011-2021
European Molecular Biology Organization
2021
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
2019
Istituti di Ricovero e Cura a Carattere Scientifico
2019
Université de Montréal
2011-2018
Inter-patient variability and the similarity of healthy leukemic stem cells (LSCs) have impeded characterization LSCs in acute myeloid leukemia (AML) their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied samples from 19 AML patients, CloneTracer revealed routes differentiation. Although residual preleukemic dominated dormant cell compartment, active resembled counterpart retained erythroid...
The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data identify predictors 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, differentiation was not predictive our patient cohort. We identified leukemic...
Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual stem might lead an insufficient graft-versus-leukemia (GVL) effect relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) lymphocytes CD34+ 6 patients with AML 100 days after allo-HCT identify T-cell signatures...
Chromatin modulators are emerging as attractive drug targets, given their widespread implication in human cancers and susceptibility to pharmacological inhibition. Here we establish the histone methyltransferase G9a/EHMT2 a selective regulator of fast proliferating myeloid progenitors with no discernible function hematopoietic stem cells (HSCs). In mouse models acute leukemia (AML), loss G9a significantly delays disease progression reduces cell (LSC) frequency. We connect this its activity...
Abstract Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the biological heterogeneity this disease. Here we report DNA methylome analysis mutation profiling 167 JMML samples. We identify three subgroups with unique molecular characteristics. The high methylation group (HM) somatic PTPN11 poor outcome. low enriched for...
Cancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization these remains elusive with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic (LSCs) underlie mortality but are difficult isolate due their low abundance high similarity healthy hematopoietic (HSCs). Here, we demonstrate that LSCs, HSCs, pre-leukemic can be identified molecularly profiled by combining single-cell transcriptomics...
The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity vivo. A comprehensive analysis the rRNA landscape 94 patients with acute myeloid (AML) revealed dynamic specifically at exterior sites ribosomes. pattern is closely associated AML stage LSC gene expression signature. Forced 2'-O-methyltransferase...
Enhancers play a vital role in gene regulation and are critical mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is cell-type-specific process regulated by transcription factors (TFs), epigenetic mechanisms variants. Despite strong mechanistic link between TFs enhancers, we currently lack framework for jointly analysing them regulatory networks (GRN). Equally important, an unbiased way assessing biological significance inferred GRNs since...
Background Multiple myeloma is a life-threatening disease and despite the introduction of stem cell transplantation novel agents such as thalidomide, lenalidomide, bortezomib most patients will relapse develop chemoresistant disease. Therefore, alternative therapeutic modes for are needed cancer-testis antigens MAGE-C1/CT7 MAGE-A3 have been suggested to represent class tumor-specific proteins particularly suited targeted immunotherapies. Surprisingly, biological role genes in remains poorly...
Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% all targets marketed drugs. Using next-generation sequencing, we studied expression 772 GPCRs in 148 genetically diverse AML specimens, normal blood bone marrow cell populations as well cord blood-derived CD34-positive cells. Among these receptors,...
Recently, high numbers of regulatory T cells within the stem cell graft were described to be associated with less graft-versus-host disease (GVHD) after related peripheral blood transplantation (PBSCT). Studies in mice also suggest a distinct role gamma delta TCR(+) mediating GVHD. Therefore, aim this study was define yet-unknown and human PBSCT from unrelated donors.The frequency both T-cell subsets analyzed 63 patients receiving allogeneic PBSCT. The respective amounts quantified by flow...