Article
Cell Biology
Branco M. H. Heuts, Saioa Arza-Apalategi, Sinne G. Alkema, Esther Tijchon, Laura Jussen, Saskia M. Bergevoet, Bert A. van der Reijden, Joost H. A. Martens
Summary: A translocation at 9;11(p22;q23) leads to the formation of MLL-AF9 fusion protein, which is found in 25% of de novo AML cases in children. Using a hiPSC model with doxycycline-dependent MLL-AF9 expression, we investigated the effects of MLL-AF9 on hematopoietic development and its transformation to (pre-)leukemic states. We observed disruptions in early myelomonocytic development and identified gene profiles consistent with primary MLL-AF9 AML.
Article
Oncology
Adam Azlan, Kang Zi Khor, Yaashini Rajasegaran, Aliaa Arina Rosli, Mohamed Saifulaman Mohamed Said, Narazah Mohd Yusoff, Emmanuel Jairaj Moses
Summary: In t(8;21) AML, RUNX1/ETO directly controls FLT3 and mediates ROS regulation by occupying DNA elements on the FLT3 locus. Suppression of RUNX1/ETO leads to decreased ROS levels and FOXO3 expression, but not FLT3 and RAC1. Nuclear import of RUNX1/ETO is aberrated following its suppression, suggesting its association in ROS control. In non t(8;21) cells, suppression of RAC1 and FLT3 decreases FOXO3a and ROS levels. These results indicate a possible dysregulation of ROS levels by RUNX1/ETO in t(8;21) AML.
Article
Oncology
Signe Neldeborg, Johannes Frasez Soerensen, Charlotte Thornild Moller, Marie Bill, Zongliang Gao, Rasmus O. Bak, Kasper Holm, Boe Sorensen, Mette Nyegaard, Yonglun Luo, Peter Hokland, Magnus Stougaard, Maja Ludvigsen, Christian Kanstrup Holm
Summary: Oncogenic fusion drivers in hematological cancers can be targeted using a new dual intron-targeting CRISPR-Cas9 treatment strategy. This strategy can efficiently disrupt fusion genes without requiring precise knowledge of the breakpoints in t(8;21) AML. In vitro and in vivo experiments showed significant reduction in cell growth and tumor growth in response to disruption of RUNX1-RUNX1T1. These findings were confirmed in primary cells from an AML patient.
Article
Allergy
Alexander Vargas-Hernandez, Agnieszka Witalisz-Siepracka, Michaela Prchal-Murhpy, Klara Klein, Sanjana Mahapatra, Waleed Al-Herz, Emily M. Mace, Alexandre F. Carisey, Jordan S. Orange, Veronika Sexl, Lisa R. Forbes
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2020)
Article
Multidisciplinary Sciences
Frank Michael Lehmann, Nicole von Burg, Robert Ivanek, Claudia Teufel, Edit Horvath, Annick Peter, Gleb Turchinovich, Daniel Staehli, Tobias Eichlisberger, Mercedes Gomez de Aguero, Mairene Coto-Llerena, Michaela Prchal-Murphy, Veronika Sexl, Mohamed Bentires-Alj, Christoph Mueller, Daniela Finke
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Gerwin Heller, Sofie Nebenfuehr, Florian Bellutti, Huriye Uenal, Markus Zojer, Lisa Scheiblecker, Veronika Sexl, Karoline Kollmann
Article
Hematology
Eszter Doma, Isabella Maria Mayer, Tania Brandstoetter, Barbara Maurer, Reinhard Grausenburger, Ingeborg Menzl, Markus Zojer, Andrea Hoelbl-Kovacic, Leif Carlsson, Gerwin Heller, Karoline Kollmann, Veronika Sexl
Summary: A robust method has been developed to generate and maintain LSK cells that closely resemble MPP1 cells, allowing for the study of hematopoiesis and leukemogenesis. By transforming these cells with different oncogenes, including BCR/ABL, FLT3-ITD, or MLL-AF9, researchers have demonstrated the importance of CDK6 in leukemia formation and identified novel CDK6-dependent pathways. The HPCLSK system provides a unique tool for in vitro and in vivo studies of hematopoietic or leukemic stem/progenitor cells.
Review
Chemistry, Medicinal
Lisa Scheiblecker, Karoline Kollmann, Veronika Sexl
Article
Hematology
Sebastian Kollmann, Reinhard Grausenburger, Thorsten Klampfl, Michaela Prchal-Murphy, Klavdija Bastl, Hanja Pisa, Vanessa M. Knab, Tania Brandstoetter, Eszter Doma, Wolfgang R. Sperr, Sabine Lagger, Matthias Farlik, Richard Moriggl, Peter Valent, Florian Halbritter, Karoline Kollmann, Gerwin Heller, Barbara Maurer, Veronika Sexl
Summary: STAT5B plays a unique role in driving self-renewal of hematopoietic and leukemic stem cells, specifically activating genes associated with quiescence and self-renewal, including CD9. CD9 levels serve as a prognostic marker for patients with STAT5-driven leukemia, and anti-CD9 antibodies may be useful in targeting and eliminating leukemic stem cells. Consideration of STAT5A and STAT5B as distinct entities is crucial in normal and malignant hematopoiesis.
Review
Oncology
Klara Klein, Dagmar Stoiber, Veronika Sexl, Agnieszka Witalisz-Siepracka
Summary: The JAK-STAT pathway is aberrantly activated in many cancers, and inhibition of this pathway via JAK inhibitors suppresses the immune system. This review article provides an overview of the effects of JAKinibs on immune cells in hematological malignancies and discusses their potential use in diseases where lymphocytes are the source of malignancy. A robust immune profiling is necessary to maximize the benefit for JAKinib-treated patients.
Review
Oncology
Isabella Maria Mayer, Andrea Hoelbl-Kovacic, Veronika Sexl, Eszter Doma
Summary: Transplantation of adult hematopoietic stem cells is crucial for treating hematological disorders, while leukemic stem cells play a significant role in disease initiation and relapse. Understanding methods to maintain and expand hematopoietic cells, as well as isolate and enrich hematopoietic stem cells and leukemic stem cells, is essential for developing therapeutic strategies.
Review
Oncology
Alessia Schirripa, Veronika Sexl, Karoline Kollmann
Summary: The cell cycle is controlled by CDKs, and dysregulation of CDK inhibitors is associated with neoplastic transformation, especially in hematological malignancies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Judith Lind, Roland Hellinger, Petra Kudweis, Herwig P. Moll, Jasmin Gattringer, Kathrin Thell, Sophie Edtmayer, Christian W. Gruber, Dagmar Stoiber, Karoline Kollmann
Summary: This study found that cyclotide-based compound T20K and its analogs have an inhibitory effect on the proliferation of anaplastic large cell lymphoma, inducing apoptosis and cell cycle arrest through increased STAT5 and p53 signaling. Mouse experiments showed promising activity of T20K on cancer cells, providing new insights for the treatment of ALCL.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Hematology
Peter Valent, Alberto Orfao, Stefan Kubicek, Philipp Staber, Torsten Haferlach, Michael Deininger, Karoline Kollmann, Thomas Lion, Irene Virgolini, Georg Winter, Oliver Hantschel, Lukas Kenner, Johannes Zuber, Florian Grebien, Richard Moriggl, Gregor Hoermann, Olivier Hermine, Michael Andreeff, Christoph Bock, Tariq Mughal, Stefan N. Constantinescu, Robert Kralovics, Veronika Sexl, Radek Skoda, Giulio Superti-Furga, Ulrich Jaeger
Summary: As our understanding of molecular mechanisms and cellular interactions in malignant blood cell disorders has improved, precision medicine and personalized medicine have become important disciplines supporting clinicians in making accurate diagnoses, predicting outcomes, and selecting optimal interventional therapies for patients. However, there are still many questions surrounding the implementation and affordability of precision medicine tools in healthcare systems, as well as the need to define and relate specific terminologies and strategies in basic and applied science.
Article
Hematology
Angela Schumich, Michaela Prchal-Murphy, Margarita Maurer-Granofszky, Andrea Hoelbl-Kovacic, Nora Muehlegger, Ulrike Poetschger, Sabine Fajmann, Oskar A. Haas, Karin Nebral, Nils von Neuhoff, Martin Zimmermann, Heidrun Boztug, Mareike Rasche, Marlies Dolezal, Christiane Walter, Dirk Reinhardt, Veronika Sexl, Michael N. Dworzak
