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Leukemic stem cells hijack lineage inappropriate signalling pathways to promote growth [DNase1-seq]

ABSTRACT: Leukemic stem cells hijack lineage inappropriate signalling pathways to promote growth [DNase1-seq]

PROVIDER: PRJNA940721 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23698793.fastq.gz	Fastqsanger.gz
	SRR23698794.fastq.gz	Fastqsanger.gz

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Leukemic stem cells hijack lineage inappropriate signalling pathways to promote growth [DNase1-seq]

Project description:Acute Myeloid Leukemia (AML) is caused by different mutations which affect growth and differentiation of myeloid cells. Depending on the mutation sub-type, cells adopt different gene regulatory networks 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 cells (leukemic stem cells or LSCs) which escape chemotherapy and can emerge from quiescence to trigger a relapse. The signalling processes that allow such cells to re-grow remain unknown. Here, we examined the well characterised t(8;21) AML sub-type as model to address this question. We show that t(8;21) LSCs aberrantly activate the ectopic VEGF and IL-5 signalling pathways. We uncovered a regulatory circuit consisting of the driver oncoprotein RUNX1-ETO and the AP-1 / GATA2 transcription factor axis allowing LSCs to re-enter the cell cycle.

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