A5080023449- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- RNA modifications and cancer
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Telomeres, Telomerase, and Senescence
- Multiple Myeloma Research and Treatments
- Advanced Proteomics Techniques and Applications
- Immune responses and vaccinations
- Lymphoma Diagnosis and Treatment
- RNA Research and Splicing
- Cell Image Analysis Techniques
- Pharmaceutical studies and practices
Heidelberg University
2015-2025
University Hospital Heidelberg
2020-2025
German Cancer Research Center
2013-2022
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2012-2021
DKFZ-ZMBH Alliance
2014-2020
Deutschen Konsortium für Translationale Krebsforschung
2015
Max Planck Society
2013
Auguste-Viktoria-Klinik
2009
Abstract Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost and a lack strategies for the purification newly identified cell types impede their functional characterization large-scale profiling. Here, we have generated high-content single-cell proteo-genomic reference maps human blood bone marrow that quantitatively link expression up to 197 surface markers identities biological processes across all main hematopoietic in...
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...
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...
Despite recent advances in adapting the intensity of treatment for older patients with ALL, current protocols are associated high rates early deaths, treatment-related toxicity, and dismal prognosis. We evaluated inotuzumab ozogamicin dexamethasone (Dex) as induction therapy ALL within German Multicenter Study Group Adult (GMALL).
Mutation is a fundamental process in tumorigenesis. However, the degree to which rate of somatic mutation varies across human genome and mechanistic basis underlying this variation remain be fully elucidated. Here, we performed cross-cancer comparison 402 whole genomes comprising diverse set childhood adult tumors, including both solid hematopoietic malignancies. Surprisingly, found that inactive X chromosome many female cancer accumulates on average twice up four times as mutations per...
Summary Current approaches to lineage tracing of stem cell clones require genetic engineering or rely on sparse somatic DNA variants, which are difficult capture at single-cell resolution. Here, we show that targeted measurements methylation single-CpG resolution deliver joint information about cellular differentiation state and clonal identities. We develop EPI-clone, a droplet-based method for transgene-free tracing, apply it study hematopoiesis, capturing hundreds trajectories across...
Abstract In contrast to B-cell precursor acute lymphoblastic leukemia (ALL), molecular subgroups are less well defined in T-lineage ALL. Comprehensive studies on T-ALL have been predominantly performed pediatric ALL patients. Currently, characteristics rarely considered for risk stratification. Herein, we present a homogenously treated cohort of 230 adult patients characterized transcriptome, and partly DNA methylation gene mutation level correlation with clinical outcome. We identified nine...
Regenerative tissues such as the skin epidermis, intestinal mucosa or hematopoietic system are organized in a hierarchical manner with stem cells building top of this hierarchy. Somatic harbor highest self-renewal activity and generate series multipotent progenitors which differentiate into lineage committed subsequently mature cells. In report, we applied an in-depth quantitative proteomic approach to analyze compare full proteomes ex vivo isolated FACS-sorted populations highly enriched...
Abstract Persistence of minimal residual disease (MRD) after induction/consolidation therapy in acute lymphoblastic leukemia is the leading cause relapse. The GMALL 07/2003 study used MRD detection by real-time quantitative polymerase chain reaction clonal immune gene rearrangements with 1 × 10−4 as discriminating cutoff: levels ≥1 define molecular failure and MRD-negativity an assay sensitivity at least defining complete response. clinical relevance results not fitting into these categories...
To understand the precise disease driving mechanisms in acute myeloid leukemia (AML), comparison of patient matched hematopoietic stem cells (HSC) and (LSC) is essential. In this analysis, we have examined value aldehyde dehydrogenase (ALDH) activity combination with CD34 expression for separation HSC from LSC 104 patients de novo AML. The majority AML (80 out 104) had low percentages high ALDH (ALDH(+) cells; <1.9%; ALDH-rare AML), whereas 24 relatively numerous ALDH(+) (≥1.9%;...
In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating cell frequencies to outcome we detected poor overall- disease-free survival frequencies. Serial analysis matched diagnostic follow-up samples further demonstrated that increased after chemotherapy in who achieved durable remissions. However, eventually relapsed, numbers decreased dramatically at the time...
Abstract Venetoclax/azacitidine combination therapy is effective in acute myeloid leukemia (AML) and tolerable for older, multimorbid patients. Despite promising response rates, many patients do not achieve sustained remission or are upfront refractory. Identification of resistance mechanisms additional therapeutic targets represent unmet clinical needs. By using a genome-wide CRISPR/Cas9 library screen targeting 18,053 protein- coding genes human AML cell line, various conferring to...
To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of hematopoietic stem progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging humans mice were then compared. Human specimens consist CD34+ from bone marrow, mouse (HSCs; Lin− Kit+ Sca1+ CD150+). Single-cell transcriptomic studies, functional clustering, developmental trajectory analyses performed. A significant increase multipotent 2A (MPP2A) cluster is found early HSC...