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

Autor: Kellaway SG; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. Sophie.Kellaway@nottingham.ac.uk.; Blood Cancer and Stem Cells, Centre for Cancer Sciences, School of Medicine, University of Nottingham, Nottingham, UK. Sophie.Kellaway@nottingham.ac.uk., Potluri S; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Keane P; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.; School of Biosciences, University of Birmingham, Birmingham, UK., Blair HJ; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Ames L; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Worker A; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Chin PS; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Ptasinska A; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Derevyanko PK; Princess Maxima Center of Pediatric Oncology, Utrecht, Netherlands., Adamo A; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Coleman DJL; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Khan N; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK., Assi SA; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Krippner-Heidenreich A; Princess Maxima Center of Pediatric Oncology, Utrecht, Netherlands., Raghavan M; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.; Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK., Cockerill PN; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Heidenreich O; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; Princess Maxima Center of Pediatric Oncology, Utrecht, Netherlands., Bonifer C; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. c.bonifer@bham.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 14; Vol. 15 (1), pp. 1359. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1038/s41467-024-45691-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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