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

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Standard

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal. / Schnoeder, Tina M; Schwarzer, Adrian; Jayavelu, Ashok Kumar; Hsu, Chen-Jen; Kirkpatrick, Joanna; Döhner, Konstanze; Perner, Florian; Eifert, Theresa; Huber, Nicolas; Arreba-Tutusaus, Patricia; Dolnik, Anna; Assi, Salam A; Nafria, Monica; Jiang, Lu; Dai, Yu-Ting; Chen, Zhu; Chen, Sai-Juan; Kellaway, Sophie G; Ptasinska, Anetta; Ng, Elizabeth S; Stanley, Edouard G; Elefanty, Andrew G; Buschbeck, Marcus; Bierhoff, Holger; Brodt, Steffen; Matziolis, Georg; Fischer, Klaus-Dieter; Hochhaus, Andreas; Chen, Chun-Wei; Heidenreich, Olaf; Mann, Matthias; Lane, Steven W; Bullinger, Lars; Ori, Alessandro; von Eyss, Björn; Bonifer, Constanze; Heidel, Florian H.

In: Blood, Vol. 139, No. 7, 2022, p. 1080-1097.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schnoeder, TM, Schwarzer, A, Jayavelu, AK, Hsu, C-J, Kirkpatrick, J, Döhner, K, Perner, F, Eifert, T, Huber, N, Arreba-Tutusaus, P, Dolnik, A, Assi, SA, Nafria, M, Jiang, L, Dai, Y-T, Chen, Z, Chen, S-J, Kellaway, SG, Ptasinska, A, Ng, ES, Stanley, EG, Elefanty, AG, Buschbeck, M, Bierhoff, H, Brodt, S, Matziolis, G, Fischer, K-D, Hochhaus, A, Chen, C-W, Heidenreich, O, Mann, M, Lane, SW, Bullinger, L, Ori, A, von Eyss, B, Bonifer, C & Heidel, FH 2022, 'PLCG1 is required for AML1-ETO leukemia stem cell self-renewal', Blood, vol. 139, no. 7, pp. 1080-1097. https://doi.org/10.1182/blood.2021012778

APA

Schnoeder, T. M., Schwarzer, A., Jayavelu, A. K., Hsu, C-J., Kirkpatrick, J., Döhner, K., Perner, F., Eifert, T., Huber, N., Arreba-Tutusaus, P., Dolnik, A., Assi, S. A., Nafria, M., Jiang, L., Dai, Y-T., Chen, Z., Chen, S-J., Kellaway, S. G., Ptasinska, A., ... Heidel, F. H. (2022). PLCG1 is required for AML1-ETO leukemia stem cell self-renewal. Blood, 139(7), 1080-1097. https://doi.org/10.1182/blood.2021012778

Vancouver

Schnoeder TM, Schwarzer A, Jayavelu AK, Hsu C-J, Kirkpatrick J, Döhner K et al. PLCG1 is required for AML1-ETO leukemia stem cell self-renewal. Blood. 2022;139(7):1080-1097. https://doi.org/10.1182/blood.2021012778

Author

Schnoeder, Tina M ; Schwarzer, Adrian ; Jayavelu, Ashok Kumar ; Hsu, Chen-Jen ; Kirkpatrick, Joanna ; Döhner, Konstanze ; Perner, Florian ; Eifert, Theresa ; Huber, Nicolas ; Arreba-Tutusaus, Patricia ; Dolnik, Anna ; Assi, Salam A ; Nafria, Monica ; Jiang, Lu ; Dai, Yu-Ting ; Chen, Zhu ; Chen, Sai-Juan ; Kellaway, Sophie G ; Ptasinska, Anetta ; Ng, Elizabeth S ; Stanley, Edouard G ; Elefanty, Andrew G ; Buschbeck, Marcus ; Bierhoff, Holger ; Brodt, Steffen ; Matziolis, Georg ; Fischer, Klaus-Dieter ; Hochhaus, Andreas ; Chen, Chun-Wei ; Heidenreich, Olaf ; Mann, Matthias ; Lane, Steven W ; Bullinger, Lars ; Ori, Alessandro ; von Eyss, Björn ; Bonifer, Constanze ; Heidel, Florian H. / PLCG1 is required for AML1-ETO leukemia stem cell self-renewal. In: Blood. 2022 ; Vol. 139, No. 7. pp. 1080-1097.

Bibtex

@article{c80db0e97f7941969251a2124a45ed8f,
title = "PLCG1 is required for AML1-ETO leukemia stem cell self-renewal",
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 deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein that 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+ leukemic stem cells.",
keywords = "Animals, Cell Self Renewal, Core Binding Factor Alpha 2 Subunit/genetics, Gene Expression Regulation, Leukemic, Hematopoietic Stem Cells/metabolism, Humans, Leukemia, Myeloid, Acute/genetics, Mice, Neoplastic Stem Cells/metabolism, Oncogene Proteins, Fusion/genetics, Phospholipase C gamma/genetics, Proteome, RUNX1 Translocation Partner 1 Protein/genetics, Transcriptome, Translocation, Genetic",
author = "Schnoeder, {Tina M} and Adrian Schwarzer and Jayavelu, {Ashok Kumar} and Chen-Jen Hsu and Joanna Kirkpatrick and Konstanze D{\"o}hner and Florian Perner and Theresa Eifert and Nicolas Huber and Patricia Arreba-Tutusaus and Anna Dolnik and Assi, {Salam A} and Monica Nafria and Lu Jiang and Yu-Ting Dai and Zhu Chen and Sai-Juan Chen and Kellaway, {Sophie G} and Anetta Ptasinska and Ng, {Elizabeth S} and Stanley, {Edouard G} and Elefanty, {Andrew G} and Marcus Buschbeck and Holger Bierhoff and Steffen Brodt and Georg Matziolis and Klaus-Dieter Fischer and Andreas Hochhaus and Chun-Wei Chen and Olaf Heidenreich and Matthias Mann and Lane, {Steven W} and Lars Bullinger and Alessandro Ori and {von Eyss}, Bj{\"o}rn and Constanze Bonifer and Heidel, {Florian H}",
note = "{\textcopyright} 2022 by The American Society of Hematology.",
year = "2022",
doi = "10.1182/blood.2021012778",
language = "English",
volume = "139",
pages = "1080--1097",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

RIS

TY - JOUR

T1 - PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

AU - Schnoeder, Tina M

AU - Schwarzer, Adrian

AU - Jayavelu, Ashok Kumar

AU - Hsu, Chen-Jen

AU - Kirkpatrick, Joanna

AU - Döhner, Konstanze

AU - Perner, Florian

AU - Eifert, Theresa

AU - Huber, Nicolas

AU - Arreba-Tutusaus, Patricia

AU - Dolnik, Anna

AU - Assi, Salam A

AU - Nafria, Monica

AU - Jiang, Lu

AU - Dai, Yu-Ting

AU - Chen, Zhu

AU - Chen, Sai-Juan

AU - Kellaway, Sophie G

AU - Ptasinska, Anetta

AU - Ng, Elizabeth S

AU - Stanley, Edouard G

AU - Elefanty, Andrew G

AU - Buschbeck, Marcus

AU - Bierhoff, Holger

AU - Brodt, Steffen

AU - Matziolis, Georg

AU - Fischer, Klaus-Dieter

AU - Hochhaus, Andreas

AU - Chen, Chun-Wei

AU - Heidenreich, Olaf

AU - Mann, Matthias

AU - Lane, Steven W

AU - Bullinger, Lars

AU - Ori, Alessandro

AU - von Eyss, Björn

AU - Bonifer, Constanze

AU - Heidel, Florian H

N1 - © 2022 by The American Society of Hematology.

PY - 2022

Y1 - 2022

N2 - 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 deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein that 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+ leukemic stem cells.

AB - 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 deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein that 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+ leukemic stem cells.

KW - Animals

KW - Cell Self Renewal

KW - Core Binding Factor Alpha 2 Subunit/genetics

KW - Gene Expression Regulation, Leukemic

KW - Hematopoietic Stem Cells/metabolism

KW - Humans

KW - Leukemia, Myeloid, Acute/genetics

KW - Mice

KW - Neoplastic Stem Cells/metabolism

KW - Oncogene Proteins, Fusion/genetics

KW - Phospholipase C gamma/genetics

KW - Proteome

KW - RUNX1 Translocation Partner 1 Protein/genetics

KW - Transcriptome

KW - Translocation, Genetic

U2 - 10.1182/blood.2021012778

DO - 10.1182/blood.2021012778

M3 - Journal article

C2 - 34695195

VL - 139

SP - 1080

EP - 1097

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -

ID: 301825665