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2 results on '"Michael Sterr"'

1. CSF3R T618I Collaborates With RUNX1-RUNX1T1 to Expand Hematopoietic Progenitors and Sensitizes to GLI Inhibition

Author

Anja S. Swoboda, Vanessa C. Arfelli, Anna Danese, Roland Windisch, Paul Kerbs, Enric Redondo Monte, Johannes W. Bagnoli, Linping Chen-Wichmann, Alessandra Caroleo, Monica Cusan, Stefan Krebs, Helmut Blum, Michael Sterr, Wolfgang Enard, Tobias Herold, Maria Colomé-Tatché, Christian Wichmann, and Philipp A. Greif

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Activating colony-stimulating factor-3 receptor gene (CSF3R) mutations are recurrent in acute myeloid leukemia (AML) with t(8;21) translocation. However, the nature of oncogenic collaboration between alterations of CSF3R and the t(8;21) associated RUNX1-RUNX1T1 fusion remains unclear. In CD34+ hematopoietic stem and progenitor cells from healthy donors, double oncogene expression led to a clonal advantage, increased self-renewal potential, and blast-like morphology and distinct immunophenotype. Gene expression profiling revealed hedgehog signaling as a potential mechanism, with upregulation of GLI2 constituting a putative pharmacological target. Both primary hematopoietic cells and the t(8;21) positive AML cell line SKNO-1 showed increased sensitivity to the GLI inhibitor GANT61 when expressing CSF3R T618I. Our findings suggest that during leukemogenesis, the RUNX1-RUNXT1 fusion and CSF3R mutation act in a synergistic manner to alter hedgehog signaling, which can be exploited therapeutically.

Published
2023
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2. The 4D nucleome: Evidence for a dynamic nuclear landscape based on co-aligned active and inactive nuclear compartments

Author

Barbara Hübner, Yolanda Markaki, Michael Sterr, Karsten Rippe, Marion Cremer, Thomas Cremer, Hilmar Strickfaden, Daniel Smeets, Jens Popken, and Christoph Cremer

Subjects
DNA Repair, Transcription, Genetic, Biophysics, Nuclear architecture, RNA polymerase II, Super-resolution fluorescence microscopy, Biochemistry, DNA sequencing, chemistry.chemical_compound, Hi-C, Structural Biology, Active nuclear compartment, Electron microscopy, Genetics, Animals, Humans, Compartment (development), Epigenetics, Nuclear pore, Molecular Biology, 4D nucleome, Cell Nucleus, Topologically associating domains, biology, Cell Biology, Chromatin, Cell biology, Crystallography, Gene Expression Regulation, chemistry, Inactive nuclear compartment, biology.protein, Perichromatin region, Nuclear transport, Interchromatin compartment, DNA
Abstract

Recent methodological advancements in microscopy and DNA sequencing-based methods provide unprecedented new insights into the spatio-temporal relationships between chromatin and nuclear machineries. We discuss a model of the underlying functional nuclear organization derived mostly from electron and super-resolved fluorescence microscopy studies. It is based on two spatially co-aligned, active and inactive nuclear compartments (ANC and INC). The INC comprises the compact, transcriptionally inactive core of chromatin domain clusters (CDCs). The ANC is formed by the transcriptionally active periphery of CDCs, called the perichromatin region (PR), and the interchromatin compartment (IC). The IC is connected to nuclear pores and serves nuclear import and export functions. The ANC is the major site of RNA synthesis. It is highly enriched in epigenetic marks for transcriptionally competent chromatin and RNA Polymerase II. Marks for silent chromatin are enriched in the INC. Multi-scale cross-correlation spectroscopy suggests that nuclear architecture resembles a random obstacle network for diffusing proteins. An increased dwell time of proteins and protein complexes within the ANC may help to limit genome scanning by factors or factor complexes to DNA exposed within the ANC.

Published
2015
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