Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth

Sophie G. Kellaway (), Sandeep Potluri, Peter Keane, Helen J. Blair, Luke Ames, Alice Worker, Paulynn S. Chin, Anetta Ptasinska, Polina K. Derevyanko, Assunta Adamo, Daniel J. L. Coleman, Naeem Khan, Salam A. Assi, Anja Krippner-Heidenreich, Manoj Raghavan, Peter N. Cockerill, Olaf Heidenreich and Constanze Bonifer ()
Additional contact information
Sophie G. Kellaway: University of Birmingham
Sandeep Potluri: University of Birmingham
Peter Keane: University of Birmingham
Helen J. Blair: Newcastle University
Luke Ames: University of Birmingham
Alice Worker: University of Birmingham
Paulynn S. Chin: University of Birmingham
Anetta Ptasinska: University of Birmingham
Polina K. Derevyanko: Princess Maxima Center of Pediatric Oncology
Assunta Adamo: University of Birmingham
Daniel J. L. Coleman: University of Birmingham
Naeem Khan: University of Birmingham
Salam A. Assi: University of Birmingham
Anja Krippner-Heidenreich: Princess Maxima Center of Pediatric Oncology
Manoj Raghavan: University of Birmingham
Peter N. Cockerill: University of Birmingham
Olaf Heidenreich: Newcastle University
Constanze Bonifer: University of Birmingham

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option is still chemotherapy which targets such cells. However, patients harbour a population of quiescent leukemic stem cells (LSCs) which can emerge from quiescence to trigger relapse after therapy. The processes that allow such cells to re-grow remain unknown. Here, we examine the well characterised t(8;21) AML sub-type as a model to address this question. Using four primary AML samples and a novel t(8;21) patient-derived xenograft model, we show that t(8;21) LSCs aberrantly activate the VEGF and IL-5 signalling pathways. Both pathways operate within a regulatory circuit consisting of the driver oncoprotein RUNX1::ETO and an AP-1/GATA2 axis allowing LSCs to re-enter the cell cycle while preserving self-renewal capacity.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45691-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45691-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45691-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().