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

Schnoeder, T. M.; Schwarzer, A.; Jayavelu, A. K.; Hsu, C. J.; Kirkpatrick, J.; Dohner, K.; Perner, F.; Eifert, T.; Huber, Nicolas; Arreba-Tutusaus, P.; Dolnik, A.; Assi, S. A.; Nafria, M.; Jiang, Lu; Dai, Y. T.; Chen, Zhu; Chen, S. J.; Kellaway, S. G.; Ptasinska, A.; Ng, E. S.; Stanley, E. G.; Elefanty, A. G.; Buschbeck, Marcus; Bierhoff, H.; Brodt, S.; Matziolis, G.; Fischer, K. D.; Hochhaus, A.; Chen, C. W.; Heidenreich, O.; Mann, M.; Lane, S. W.; Bullinger, L.; Ori, A.; von Eyss, B.; Bonifer, C.; Heidel, F. H.

doi:10.1182/blood.2021012778

Local TagsRelease HistoryDetailsSummary

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

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

Item is Released

show all hide all

Basic

show hide

Item Permalink: https://hdl.handle.net/21.11116/0000-000A-AAF7-0 Version Permalink: https://hdl.handle.net/21.11116/0000-000A-AAF8-F

Genre: Journal Article

Files

show Files

Locators

show

Creators

show

hide

Creators:
Schnoeder, T. M., Author
Schwarzer, A., Author
Jayavelu, A. K.¹, Author
Hsu, C. J., Author
Kirkpatrick, J., Author
Dohner, K., Author
Perner, F., Author
Eifert, T., Author
Huber, Nicolas, Author
Arreba-Tutusaus, P., Author
Dolnik, A., Author
Assi, S. A., Author
Nafria, M., Author
Jiang, Lu, Author
Dai, Y. T., Author
Chen, Zhu, Author
Chen, S. J., Author
Kellaway, S. G., Author
Ptasinska, A., Author
Ng, E. S., Author
Stanley, E. G., AuthorElefanty, A. G., AuthorBuschbeck, Marcus, AuthorBierhoff, H., AuthorBrodt, S., AuthorMatziolis, G., AuthorFischer, K. D., AuthorHochhaus, A., AuthorChen, C. W., AuthorHeidenreich, O., AuthorMann, M.¹, Author Lane, S. W., AuthorBullinger, L., AuthorOri, A., Authorvon Eyss, B., AuthorBonifer, C., AuthorHeidel, F. H., Author more..

Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159

Content

show

hide

Free keywords: acute myeloid-leukemia fusion protein t(8/21) aml inhibition expression identification plc-gamma-1 prognosis runx1/eto Hematology

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.

Details

show

hide

Language(s): eng - English

Dates: Date issued: 2022-02-17

Publication Status: Issued

Pages: -

Publishing info: -

Table of Contents: -

Rev. Type: -

Identifiers: Other: WOS:000760193300015
DOI: 10.1182/blood.2021012778
ISSN: 0006-4971

Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show

hide

Title: Blood

Other : Blood

Source Genre: Journal

Creator(s):

Affiliations:

Publ. Info: Philadelphia, Pa. : W.B. Saunders

Pages: - Volume / Issue: 139 (7) Sequence Number: - Start / End Page: 1080 - 1097 Identifier: ISSN: 0006-4971
CoNE: https://pure.mpg.de/cone/journals/resource/954925385125