A5075868698- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- RNA Research and Splicing
- Chromatin Remodeling and Cancer
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- ATP Synthase and ATPases Research
- Congenital heart defects research
- Cancer Genomics and Diagnostics
- Hematopoietic Stem Cell Transplantation
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Pancreatic function and diabetes
- Platelet Disorders and Treatments
- Eosinophilic Disorders and Syndromes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
Goethe University Frankfurt
2021-2024
Martin Luther University Halle-Wittenberg
2019-2023
Luther University
2021
Wittenberg University
2021
Freie Universität Berlin
2021
Max Planck Institute for Molecular Genetics
2021
Essen University Hospital
2021
Medizinische Hochschule Hannover
2021
Center of Regenerative Medicine in Barcelona
2016
Barcelona Biomedical Research Park
2016
Abstract Gain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia. However, it remains unclear how partial or complete amplifications Hsa21 promote leukemogenesis and why children with Down syndrome (DS) (ie, trisomy 21) are particularly at risk leukemia development. Here, we propose that RUNX1 isoform disequilibrium RUNX1A bias key to DS-associated myeloid (ML-DS). Starting Hsa21-focused CRISPR–CRISPR-associated protein 9 screens, uncovered a strong specific...
Given the plasticity of hematopoietic stem and progenitor cells, multiple routes differentiation must be blocked in pathogenesis acute myeloid leukemia, molecular basis which is incompletely understood. We report that posttranscriptional repression transcription factor ARID3A by miR-125b a key event megakaryoblastic leukemia (AMKL). AMKL frequently associated with trisomy 21 GATA1 mutations (GATA1s), children Down syndrome are at high risk developing disease. The results our study showed...
Current sources of platelets for transfusion are insufficient and associated with risk alloimmunization blood-borne infection. These limitations could be addressed by the generation autologous megakaryocytes (MKs) derived in vitro from somatic cells ability to engraft differentiate vivo. Here, we show that overexpression a defined set six transcription factors efficiently converts mouse human fibroblasts into MK-like progenitors. The transdifferentiated CD41+, display polylobulated nuclei,...
Abstract Aneuploidy is a hallmark of cancer, but its complex nature limits our understanding how it drives oncogenesis. Gain chromosome 21 (Hsa21) among the most frequent aneuploidies in leukemia and associated with markedly increased risk. Here, we propose that disequilibrium RUNX1 isoforms key to pathogenesis trisomy (i.e. Down syndrome)-associated myeloid (ML-DS). Hsa21-focused CRISPR-Cas9 screens uncovered strong specific dependency ML-DS. Mechanistic studies revealed excess RUNX1A...
Abstract The noncoding genome presents a largely untapped source of biological insights, including thousands long RNA (lncRNA) loci. While some produce bona fide lncRNAs, others exert transcript-independent cis -regulatory effects, and lack predictive features renders mechanistic dissection challenging. Here, we describe MYNRL15, CTCF-enriched lncRNA locus pan-myeloid leukemia dependency initially identified by expression-guided CRISPR interference screens. We show that accessibility...
Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Transient abnormal myelopoiesis (TAM) is a preleukemic disorder that affects 30% of newborns with Down syndrome, which can progress to (ML-DS). The current lack effective treatments for TAM due limited clinical trials and the high sensitivity trisomy 21 patients chemotherapeutic toxicity. Preventing progression from ML-DS remains significant challenge. Aims: Our goal identity treatment options prevent by...
Using a cDNA library from the chemo-resistant Hodgkin lymphoma (HL) cell line L-1236, we identified new splicing variant of human transcription factor ONECUT2 (OC2). This (OC2 s) contains single CUT domain without an associated HOX domain, which characterizes proteins ONECUT family. Expression analysis by quantitative Real Time PCR (qRT-PCR) showed high expression OC2 and s in HL lines as well normal liver tissue. In contrast, Kasumi-1, HL-60 MCF-7 testis only. The majority tissues expressed...
Down syndrome-associated myeloid leukemia is characterized by the triad of trisomy 21, fetal origin and mutations in GATA1 (GATA1 s mutations). However, synergy 21 disease initiation progression remains to be understood. Leveraging combined CRISPR-Cas9 genome editing lentiviral overexpression, we interrogated interaction Gata1 mutation with different permutations members miR-99a˜125b tricistron (miR-125b-2, miR-99a, let-7c) murine liver cells. We observed major synergistic effects...
Myeloid leukemia associated with Down syndrom (ML-DS) is characterized by the triad of fetal origin, trisomy 21 and truncating Gata1 mutations. Chromosome 21-encoded microRNAs miR-99a~125b tricistron are highly upregulated in ML-DS. We identified miR-125b as dominant microRNA within this cluster synergizing Gata1s during leukemogenesis. Combining RNA-sequencing an shRNA-based positive selection screening hematopoietic stem/progenitor cells, we Arid3a main target miR-125b, responsible for...
Down syndrome myeloid leukemia (ML-DS) is characterized by exclusive expression of an N-terminus truncated GATA1 (GATA1s) and disequilibrium RUNX1 isoform expression. ML-DS blasts are dependent on intact RUNX1, while GATA1s RUNX1A synergize to induce in mice. Here, we studied differential chromatin occupancy as well isoforms at target gene promoters their effect transcription.
Abstract Given the plasticity of hematopoietic stem/progenitor cells, multiple routes differentiation must be blocked during acute myeloid leukemia pathogenesis – molecular basis which is incompletely understood. Here we report that post-transcriptional repression transcription factor ARID3A by miR-125b a key event in megakaryoblastic (AMKL) pathogenesis. AMKL frequently associated with trisomy 21 and GATA1 mutations (GATA1s), children Down syndrome are at high risk developing this disease....
Abstract The noncoding genome presents a largely untapped source of biological insights, including thousands long RNA (lncRNA) loci. While some produce bona fide lncRNAs, others exert transcript-independent cis-regulatory effects, and the lack predictive features renders mechanistic dissection challenging. Here, we describe CTCF-enriched lncRNA loci (C-LNC) as subclass functional genetic elements exemplified by MYNRL15, pan-myeloid leukemia dependency identified an lncRNA-based CRISPRi...