Use the keywords feature with a free QxMD account.
Use Read by QxMD to access full text via your institution or open access sources.
Read also provides personalized recommendations to keep you up to date in your field.
Existing User
Sign InNew to Read
Sign Up#1
JOURNAL ARTICLE
Alexander Waclawiczek, Aino-Maija Leppä, Simon Renders, Andreas Trumpp
Acute myeloid leukemia (AML) therapy is undergoing rapid development, but primary and acquired resistance to therapy complicates the prospect of a durable cure. Recent functional and single-cell multi-omics approaches have greatly expanded our knowledge of the diversity of lineage trajectories in AML settings. AML cells range from undifferentiated stem-like cells to more differentiated myeloid or megakaryocyte/erythroid cells. Current clinically relevant drugs predominantly target the myeloid progenitor lineage, while monocyte- or stem cell-like states can evade current AML treatment and may be targeted in the future with lineage-specific inhibitors...
February 20, 2024: Molecular Oncology
#2
JOURNAL ARTICLE
Florencio Porto Freitas, Hamed Alborzinia, Ancély Ferreira Dos Santos, Palina Nepachalovich, Lohans Pedrera, Omkar Zilka, Alex Inague, Corinna Klein, Nesrine Aroua, Kamini Kaushal, Bettina Kast, Svenja M Lorenz, Viktoria Kunz, Helene Nehring, Thamara N Xavier da Silva, Zhiyi Chen, Sena Atici, Sebastian G Doll, Emily L Schaefer, Ifedapo Ekpo, Werner Schmitz, Aline Horling, Peter Imming, Sayuri Miyamoto, Ann M Wehman, Thiago C Genaro-Mattos, Karoly Mirnics, Lokender Kumar, Judith Klein-Seetharaman, Svenja Meierjohann, Isabel Weigand, Matthias Kroiss, Georg W Bornkamm, Fernando Gomes, Luis Eduardo Soares Netto, Manjima B Sathian, David B Konrad, Douglas F Covey, Bernhard Michalke, Kurt Bommert, Ralf C Bargou, Ana Garcia-Saez, Derek A Pratt, Maria Fedorova, Andreas Trumpp, Marcus Conrad, José Pedro Friedmann Angeli
Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation1,2 . Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation3 , we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells...
January 31, 2024: Nature
#3
JOURNAL ARTICLE
Nicolas Hohmann, Martin Ronald Sprick, Azaz Ahmed, Jürgen Burhenne, Marietta Kirchner, Lucian Le Cornet, Markus Kratzmann, Jacek Hajda, Albrecht Stenzinger, Karen Steindorf, Stefan Delorme, Heinz-Peter Schlemmer, Sabine Riethdorf, Ron van Schaik, Klaus Pantel, Jens Siveke, Thomas Seufferlein, Dirk Jäger, Walter E Haefeli, Andreas Trumpp, Christoph Springfeld
Expression of CYP3A5 protein is a basal and acquired resistance mechanism of pancreatic ductal adenocarcinoma cells conferring protection against the CYP3A and CYP2C8 substrate paclitaxel through metabolic degradation. Inhibition of CYP3A isozymes restores the cells sensitivity to paclitaxel. The combination of gemcitabine and nab-paclitaxel is an established regimen for the treatment of metastasized or locally advanced inoperable pancreatic cancer. Cobicistat is a CYP3A inhibitor developed for the pharmacoenhancement of protease inhibitors...
November 3, 2023: Clinical and Translational Science
#4
JOURNAL ARTICLE
Michael Neumaier, Sophie Giesler, Volker Ast, Mathis Roemer, Timo-Daniel Voß, Eileen Reinz, Victor Costina, Martin Schmelz, Elina Nürnberg, Stefanie Nittka, Aino-Maija Leppä, Ruediger Rudolf, Andreas Trumpp, Tina Fuchs
This report demonstrates a novel class of innate immune cells designated "variable immunoreceptor-expressing myeloids" (VIREMs). Using single-cell transcriptomics and genome-wide epigenetic profiling, we establish that VIREMs are myeloid cells unrelated to lymphocytes. We visualize the phenotype of B-VIREMs that are capable of genetically recombining and expressing antibody genes, the exclusive hallmark function of B lymphocytes. These cells, designated B-VIREMs, display monoclonal antibody cell surface signatures and regularly circulate in the blood of healthy individuals...
September 2023: Science Advances
#5
JOURNAL ARTICLE
Hamed Alborzinia, Zhiyi Chen, Umut Yildiz, Florencio Porto Freitas, Felix C E Vogel, Julianna Patricia Varga, Jasmin Batani, Christoph Bartenhagen, Werner Schmitz, Gabriele Büchel, Bernhard Michalke, Jashuo Zheng, Svenja Meierjohann, Enrico Girardi, Elisa Espinet, Andrés F Flórez, Ancely Ferreira Dos Santos, Nesrine Aroua, Tasneem Cheytan, Julie Haenlin, Lisa Schlicker, Thamara N Xavier da Silva, Adriana Przybylla, Petra Zeisberger, Giulio Superti-Furga, Martin Eilers, Marcus Conrad, Marietta Fabiano, Ulrich Schweizer, Matthias Fischer, Almut Schulze, Andreas Trumpp, José Pedro Friedmann Angeli
Ferroptosis has emerged as an attractive strategy in cancer therapy. Understanding the operational networks regulating ferroptosis may unravel vulnerabilities that could be harnessed for therapeutic benefit. Using CRISPR-activation screens in ferroptosis hypersensitive cells, we identify the selenoprotein P (SELENOP) receptor, LRP8, as a key determinant protecting MYCN-amplified neuroblastoma cells from ferroptosis. Genetic deletion of LRP8 leads to ferroptosis as a result of an insufficient supply of selenocysteine, which is required for the translation of the antiferroptotic selenoprotein GPX4...
July 12, 2023: EMBO Molecular Medicine
#6
JOURNAL ARTICLE
Marie Schneider, Clara Rolfs, Matthias Trumpp, Susann Winter, Luise Fischer, Mandy Richter, Victoria Menger, Kolja Nenoff, Nora Grieb, Klaus H Metzeler, Anne Sophie Kubasch, Katja Sockel, Christian Thiede, Jincheng Wu, Janghee Woo, Andreas Brüderle, Lorenz C Hofbauer, Jörg Lützner, Andreas Roth, Michael Cross, Uwe Platzbecker
Aberrant innate immune signaling has been identified as a potential key driver of the complex pathophysiology of myelodysplastic neoplasms (MDS). This study of a large, clinically and genetically well-characterized cohort of treatment-naïve MDS patients confirms intrinsic activation of inflammatory pathways in general mediated by caspase-1, interleukin (IL)-1β and IL-18 in low-risk (LR)-MDS bone marrow and reveals a previously unrecognized heterogeneity of inflammation between genetically defined LR-MDS subgroups...
July 7, 2023: Leukemia
#7
JOURNAL ARTICLE
Katharina Weidenauer, Christina Schmidt, Christian Rohde, Cornelius Pauli, Maximilian F Blank, Daniel Heid, Alexander Waclawiczek, Anika Corbacioglu, Stefanie Göllner, Michelle Lotze, Lisa Vierbaum, Simon Renders, Jeroen Krijgsveld, Simon Raffel, Tim Sauer, Andreas Trumpp, Caroline Pabst, Carsten Müller-Tidow, Maike Janssen
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 and additional therapeutic targets represent unmet clinical needs. By using a genome-wide CRISPR/Cas9 library screen targeting 18,053 protein- coding genes in a human AML cell line, various genes conferring resistance to combined venetoclax/azacitidine treatment were identified...
August 2023: Leukemia
#8
JOURNAL ARTICLE
Patrick Stelmach, Sarah Richter, Sandra Sauer, Margarete A Fabre, Muxin Gu, Christian Rohde, Maike Janssen, Nora Liebers, Rumyana Proynova, Niels Weinhold, Marc S Raab, Hartmut Goldschmidt, Birgit Besenbeck, Petra Pavel, Sascha Laier, Andreas Trumpp, Sascha Dietrich, George S Vassiliou, Carsten Müller-Tidow
Clonal hematopoiesis (CH) is an age-related condition driven by stem- and progenitor cells harboring recurrent mutations linked to myeloid neoplasms. Currently, potential effects on hematopoiesis, stem cell function and regenerative potential under stress conditions are unknown. We performed targeted DNA sequencing of 457 hematopoietic stem cell grafts collected for autologous stem cell transplantation (ASCT) in myeloma patients and correlated our findings with high-dimensional longitudinal clinical and laboratory data (26,510 data points for blood cell counts/serum values in 25 days around transplantation)...
June 29, 2023: Haematologica
#9
JOURNAL ARTICLE
Massimo Saini, Laura Schmidleitner, Helena Domínguez Moreno, Elisa Donato, Mattia Falcone, Johanna M Bartsch, Vanessa Vogel, Roberto Würth, Nicole Pfarr, Elisa Espinet, Mareike Lehmann, Melanie Königshoff, Manuel Reitberger, Simon Haas, Elisabeth Graf, Thomas Schwarzmayr, Tim-Matthias Strom, Saskia Spaich, Marc Sütterlin, Andreas Schneeweiss, Wilko Weichert, Gunnar Schotta, Maximilian Reichert, Nicola Aceto, Martin R Sprick, Andreas Trumpp, Christina H Scheel, Corinna Klein
The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively...
May 30, 2023: Cell Reports
#10
JOURNAL ARTICLE
Shiva Bamezai, Alex Jose Pulikkottil, Tribhuwan Yadav, Naidu M Vegi, Julia Mueller, Jasmin Mark, Tamoghna Mandal, Kristin Feder, Susann Ihme, Chenlin Song, Reinhild Rosler, Sebastian Wiese, Jessica I Hoell, Andreas Kloetgen, Aly Karsan, Ankita Kumari, Luke Wojenski, Amit U Sinha, Irene Gonzalez-Menendez, Leticia Quintanilla-Martinez, Elisa Donato, Andreas Trumpp, Elisabeth Kruse, Stephan Hamperl, Lee Zou, Vijay P S Rawat, Christian Buske
RNA-binding proteins (RBPs) form a large and diverse class of factors, many members of which are overexpressed in hematologic malignancies. RBPs participate in various processes of messenger RNA (mRNA) metabolism and prevent harmful DNA:RNA hybrids or R-loops. Here, we report that PIWIL4, a germ stem cell-associated RBP belonging to the RNase H-like superfamily, is overexpressed in patients with acute myeloid leukemia (AML) and is essential for leukemic stem cell function and AML growth, but dispensable for healthy human hematopoietic stem cells...
July 6, 2023: Blood
#11
JOURNAL ARTICLE
Hanif J Khameneh, Nicolas Fonta, Alessandro Zenobi, Charlène Niogret, Pedro Ventura, Concetta Guerra, Ivo Kwee, Andrea Rinaldi, Matteo Pecoraro, Roger Geiger, Andrea Cavalli, Francesco Bertoni, Eric Vivier, Andreas Trumpp, Greta Guarda
MYC is a pleiotropic transcription factor involved in cancer, cell proliferation, and metabolism. Its regulation and function in NK cells, which are innate cytotoxic lymphocytes important to control viral infections and cancer, remain poorly defined. Here, we show that mice deficient for Myc in NK cells presented a severe reduction in these lymphocytes. Myc was required for NK cell development and expansion in response to the key cytokine IL-15, which induced Myc through transcriptional and posttranslational mechanisms...
July 2023: Life Science Alliance
#12
JOURNAL ARTICLE
Sergi Beneyto-Calabuig, Anne Kathrin Merbach, Jonas-Alexander Kniffka, Magdalena Antes, Chelsea Szu-Tu, Christian Rohde, Alexander Waclawiczek, Patrick Stelmach, Sarah Gräßle, Philip Pervan, Maike Janssen, Jonathan J M Landry, Vladimir Benes, Anna Jauch, Michaela Brough, Marcus Bauer, Birgit Besenbeck, Julia Felden, Sebastian Bäumer, Michael Hundemer, Tim Sauer, Caroline Pabst, Claudia Wickenhauser, Linus Angenendt, Christoph Schliemann, Andreas Trumpp, Simon Haas, Michael Scherer, Simon Raffel, Carsten Müller-Tidow, Lars Velten
Inter-patient variability and the similarity of healthy and leukemic stem cells (LSCs) have impeded the characterization of LSCs in acute myeloid leukemia (AML) and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 AML patients, CloneTracer revealed routes of leukemic differentiation. Although residual healthy and preleukemic cells dominated the dormant stem cell compartment, active LSCs resembled their healthy counterpart and retained erythroid capacity...
April 19, 2023: Cell Stem Cell
#13
JOURNAL ARTICLE
Lena Wiedmann, Francesca De Angelis Rigotti, Nuria Vaquero-Siguero, Elisa Donato, Elisa Espinet, Iris Moll, Elisenda Alsina-Sanchis, Hanibal Bohnenberger, Elena Fernandez-Florido, Ronja Mülfarth, Margherita Vacca, Jennifer Gerwing, Lena-Christin Conradi, Philipp Ströbel, Andreas Trumpp, Carolin Mogler, Andreas Fischer, Juan Rodriguez-Vita
Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis. Bioinformatic analysis showed that HAPLN1 expression is enriched in the basal PDAC subtype and associated with worse overall patient survival...
April 24, 2023: Nature Communications
#14
JOURNAL ARTICLE
Dawn S Lin, Andreas Trumpp
Endothelial protein C receptor (EPCR) has emerged as one of the most conserved and reliable surface markers for the prospective identification and isolation of hematopoietic stem cells (HSCs). Prior studies have consistently demonstrated that EPCR expression enriches HSCs capable of long-term multilineage repopulation in both mouse and human across different hematopoietic tissues, including bone marrow (BM), fetal liver and ex vivo HSC expansion cultures. However, little is known about the expression profiles of EPCR in multipotent progenitor (MPP) populations located immediately downstream of HSCs in the hematopoietic hierarchy and which play a major role in sustaining lifelong blood cell production...
June 2023: Cells & development
#15
JOURNAL ARTICLE
Kai Bartkowiak, Parinaz Mossahebi Mohammadi, Sebastian Gärtner, Marcel Kwiatkowski, Antje Andreas, Maria Geffken, Sven Peine, Karl Verpoort, Ursula Scholz, Thomas M Deutsch, Laura L Michel, Andreas Schneeweiss, Verena Thewes, Andreas Trumpp, Volkmar Müller, Sabine Riethdorf, Hartmut Schlüter, Klaus Pantel
In cancer metastasis, single circulating tumor cells (CTCs) in the blood and disseminated tumor cells (DTCs) in the bone marrow mediate cancer metastasis. Because suitable biomarker proteins are lacking, CTCs and DTCs with mesenchymal attributes are difficult to isolate from the bulk of normal blood cells. To establish a procedure allowing the isolation of such cells, we analyzed the cell line BC-M1 established from DTCs in the bone marrow of a breast cancer patient by stable isotope labeling by amino acids in cell culture (SILAC) and mass spectrometry...
March 16, 2023: Journal of Proteome Research
#16
JOURNAL ARTICLE
Takehiro Miyazaki, Mito Kanatsu-Shinohara, Narumi Ogonuki, Shogo Matoba, Atsuo Ogura, Chihiro Yabe-Nishimura, Hongliang Zhang, Yves Pommier, Andreas Trumpp, Takashi Shinohara
Reactive oxygen species (ROS) are generated from NADPH oxidases and mitochondria; they are generally harmful for stem cells. Spermatogonial stem cells (SSCs) are unique among tissue-stem cells because they undergo ROS-dependent self-renewal via NOX1 activation. However, the mechanism by which SSCs are protected from ROS remains unknown. Here, we demonstrated a critical role of Gln in ROS protection using cultured SSCs derived from immature testes. Measurements of amino acids required for SSC cultures revealed the indispensable role of Gln in SSC survival...
March 8, 2023: Development
#17
JOURNAL ARTICLE
Alexander Waclawiczek, Aino-Maija Leppa, Simon Renders, Karolin Stumpf, Cecilia Reyneri, Barbara Betz, Maike Janssen, Rabia Shahswar, Elisa Donato, Darja Karpova, Vera Thiel, Julia M Unglaub, Susanna Grabowski, Stefanie Gryzik, Lisa Vierbaum, Richard F Schlenk, Christoph Rollig, Michael Hundemer, Caroline Pabst, Michael Heuser, Simon Raffel, Carsten Muller-Tidow, Tim Sauer, Andreas Trumpp
The BCL-2 inhibitor Venetoclax (VEN) in combination with Azacitidine (5-AZA) is currently transforming Acute Myeloid Leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined therapy outcome...
March 9, 2023: Cancer Discovery
#18
REVIEW
Patrick Stelmach, Andreas Trumpp
A major obstacle in the treatment of acute myeloid leukemia (AML) is refractory disease or relapse after achieving remission. The latter arises from a few therapy-resistant cells within minimal residual disease (MRD). Resistant cells with long-term self-renewal capacity that drive clonal outgrowth are referred to as leukemic stem cells (LSC). The cancer stem cell concept considers LSC as relapse-initiating cells residing at the top of each genetically defined AML subclone forming epigenetically controlled downstream hierarchies...
February 1, 2023: Haematologica
#19
JOURNAL ARTICLE
Elisa Donato, Nadia C Correia, Carolin Andresen, Darja Karpova, Roberto Würth, Corinna Klein, Markus Sohn, Adriana Przybylla, Petra Zeisberger, Kathrin Rothfelder, Helmut R Salih, Halvard Bonig, Sebastian Stasik, Christoph Röllig, Anna Dolnik, Lars Bullinger, Frank Buchholz, Christian Thiede, Daniel Hübschmann, Andreas Trumpp
AML is a heterogeneous disease characterized by high rate of relapse and mortality. While chemotherapies may eradicate blasts, they are less effective in eliminating relapse-causing Leukemic Stem Cells (LSCs). Although LSCs are usually identified as CD34+CD38- cells, there is significant heterogeneity in surface marker expression and CD34- LSCs exist particularly in NPM1mut AMLs. By analyzing diagnostic primary DNMT3AmutNPM1mut AML samples, we suggest a novel flow cytometry sorting strategy particularly useful for CD34neg AML subtypes...
December 1, 2022: Blood Advances
#20
JOURNAL ARTICLE
Fengbiao Zhou, Nesrine Aroua, Yi Liu, Christian Rohde, Jingdong Cheng, Anna-Katharina Wirth, Daria Fijalkowska, Stefanie Göllner, Michelle Lotze, Haiyang Yun, Xiaobing Yu, Caroline Pabst, Tim Sauer, Thomas Oellerich, Hubert Serve, Christoph Rollig, Martin Bornhauser, Christian Thiede, Claudia Baldus, Michaela Frye, Simon Raffel, Jeroen Krijgsveld, Irmela Jeremias, Roland Beckmann, Andreas Trumpp, Carsten Muller-Tidow
The development and regulation of malignant self-renewal remains an unresolved issue. Here, we provide biochemical, genetic, and functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity in vivo. A comprehensive analysis of the rRNA 2'-O-methylation landscape of 94 acute myeloid leukemia (AML) patients revealed dynamic 2'-O-methylation specifically at exterior sites of ribosomes. rRNA 2'-O-methylation pattern is closely associated with AML development stage and LSC gene expression signature...
October 19, 2022: Cancer Discovery
Make the most of Read.
Download the mobile app.
Download the mobile app.
Fetching more papers... 
