PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Tina M Schnoeder; Adrian Schwarzer; Ashok Kumar Jayavelu; Chen-Jen Hsu; Joanna Kirkpatrick; Konstanze Döhner; Florian Perner; Theresa Eifert; Nicolas Huber; Patricia Arreba-Tutusaus; Anna Dolnik; Salam A Assi; Monica Nafria; Lu Jiang; Yu-Ting Dai; Zhu Chen; Sai-Juan Chen; Sophie G Kellaway; Anetta Ptasinska; Elizabeth S Ng; Edouard G Stanley; Andrew G Elefanty; Marcus Buschbeck; Holger Bierhoff; Steffen Brodt; Georg Matziolis; Klaus-Dieter Fischer; Andreas Hochhaus; Chun-Wei Chen; Olaf Heidenreich; Matthias Mann; Steven W Lane; Lars Bullinger; Alessandro Ori; Björn von Eyss; Constanze Bonifer; Florian Heidel

doi:10.1182/blood.2021012778

Back

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Journal article

Peer reviewed

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Tina M Schnoeder, Adrian Schwarzer, Ashok Kumar Jayavelu, Chen-Jen Hsu, Joanna Kirkpatrick, Konstanze Döhner, Florian Perner, Theresa Eifert, Nicolas Huber, Patricia Arreba-Tutusaus, …

Blood

10/25/2021

DOI: https://doi.org/10.1182/blood.2021012778

PMID: 34695195

Abstract

In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a de-regulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells.

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Metrics

24 Record Views

See more details

Details

Title: PLCG1 is required for AML1-ETO leukemia stem cell self-renewal
Creators: Tina M Schnoeder - Universitätsmedizin Greifswald, Greifswald, Germany
Adrian Schwarzer - Hannover Medical School, Hannover, Germany
Ashok Kumar Jayavelu - Max Planck Institute of Biochemistry, München, Germany
Chen-Jen Hsu - Universitätsmedizin Greifswald, Greifswald, Germany
Joanna Kirkpatrick - Leibniz Institute on Aging, Jena, Germany
Konstanze Döhner - University Hospital of Ulm, Ulm, Germany
Florian Perner - Universitätsmedizin Greifswald, Germany
Theresa Eifert - Universitätsmedizin Greifswald, Greifswald, Germany
Nicolas Huber - Universitätsmedizin Greifswald, Greifswald, Germany
Patricia Arreba-Tutusaus - University Hospital Tübingen, Tübingen, Germany
Anna Dolnik - Charité University Medicine, Berlin, Germany
Salam A Assi - University of Birmingham, Leeds, United Kingdom
Monica Nafria - University of Birmingham, Birmingham, United Kingdom
Lu Jiang - Shanghai Institute of Hematology, Shanghai, China
Yu-Ting Dai - Shanghai Institute of Hematology, Shanghai, China
Zhu Chen - Shanghai Institute of Hematology, Shanghai, China
Sai-Juan Chen - Shanghai Jiao Tong University School of Medicine, Shanghai, China
Sophie G Kellaway - University of Birmingham, Birmingham, United Kingdom
Anetta Ptasinska - University of Birmingham, Birmingham, United Kingdom
Elizabeth S Ng - Murdoch Childrens Research Institute, Parkville, Australia
Edouard G Stanley - University of Melbourne, Australia
Andrew G Elefanty - University of Melbourne, Australia
Marcus Buschbeck - Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain
Holger Bierhoff - Friedrich-Schiller University, Jena, Germany
Steffen Brodt - University Hospital Jena, Campus Eisenberg, Eisenberg, Germany
Georg Matziolis - University Hospital Jena, Campus Eisenberg, Eisenberg, Germany
Klaus-Dieter Fischer - Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Andreas Hochhaus - Universitätsklinikum Jena, Jena, Germany
Chun-Wei Chen - City of Hope, Duarte, California, United States
Olaf Heidenreich - University of Newcastle, United Kingdom
Matthias Mann - Max-Planck Institute for Biochemistry, Martinsried, Germany
Steven W Lane - Queensland Institute of Medical Research, Brisbane, Australia
Lars Bullinger - Charité University Medicine, Berlin, Germany
Alessandro Ori - Leibniz Institute on Aging, Jena, Germany
Björn von Eyss - Leibniz Institute on Aging, Fritz Lipmann Institute e.V, Jena, Germany
Constanze Bonifer - University of Birmingham, Birmingham, United Kingdom
Florian Heidel - Universitätsklinikum Jena, Germany
Publication Details: Blood
Publisher: American Society of Hematology
Identifiers: 9924050515801921
Academic Unit: Rosenstiel Basic Medical Sciences Research Center; Department of Biology
Language: English
Resource Type: Journal article

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Abstract

UN Sustainable Development Goals (SDGs)

Metrics

Details

Brandeis University Social media