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Integrated high-throughput screen to identify novel treatment leads for pediatric acute myeloid leukemia (AML)

ABSTRACT: Integrated high-throughput screen to identify novel treatment leads for pediatric acute myeloid leukemia (AML)

PROVIDER: PRJNA522070 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8570240_1.fastq.gz	Fastqsanger.gz
	SRR8570240_2.fastq.gz	Fastqsanger.gz
	SRR8570241_1.fastq.gz	Fastqsanger.gz
	SRR8570241_2.fastq.gz	Fastqsanger.gz
	SRR8570242_1.fastq.gz	Fastqsanger.gz

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Integrated high-throughput screen to identify novel treatment leads for pediatric acute myeloid leukemia (AML)

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Project description:MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21), inv(16) or MLL-rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL-rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21) (n=21), inv(16) (n=17) or MLL-rearrangement (n=35) by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases, which also included 12 t(15;17) and 5 t(7;12) samples.

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