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Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities [DSP601-649-749]

ABSTRACT: Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities [DSP601-649-749]

PROVIDER: PRJNA858492 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20171700_1.fastq.gz	Fastqsanger.gz
	SRR20171700_2.fastq.gz	Fastqsanger.gz
	SRR20171701_1.fastq.gz	Fastqsanger.gz
	SRR20171701_2.fastq.gz	Fastqsanger.gz
	SRR20171702_1.fastq.gz	Fastqsanger.gz

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Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities [DSP601-649-749]

Project description:Pediatric acute megakaryoblastic leukemia (AMKL) is an aggressive blood cancer associated with poor therapeutic response and high mortality. We developed CBFA2T3-GLIS2-driven mouse models of AMKL that recapitulate the phenotypic and transcriptional signatures of the human disease. We show that CBFA2T3-GLIS2 and GLIS2 modulate similar transcriptional networks. Oncogenic RAS cooperates with GLIS2 to trigger AMKL, enhancing the penetrance and decreasing the latency of CBFA2T3-GLIS2-dependent AMKL. We find that the FDA-approved drug pyrvinium pamoate, a GLI protein inhibitor, can be repurposed to impair CBFA2T3-GLIS2 levels and promote AMKL cell death. In addition, consistent with our findings that both CBFA2T3-GLIS2 and GLIS2 alter the expression of numerous BH3-only proteins, murine and patient-derived AMKL cells are sensitive to the BCL-2 inhibitor navitoclax. We observe a striking synergistic response to combined treatment with pyrvinium pamoate and navitoclax, suggesting a novel therapeutic option for pediatric patients suffering from CBFA2T3-GLIS2-driven AMKL.

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Project description:Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities

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Project description:Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities [DSP750]

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Project description:This SuperSeries is composed of the following subset Series: GSE35201: Transcriptome Sequence Analysis of Pediatric Acute Megakaryoblastic Leukemia Identifies An Inv(16)(p13.3;q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein As a Recurrent Lesion in 39% of Non-Infant Cases [2007] GSE35202: Transcriptome Sequence Analysis of Pediatric Acute Megakaryoblastic Leukemia Identifies An Inv(16)(p13.3;q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein As a Recurrent Lesion in 39% of Non-Infant Cases [2010] Refer to individual Series

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Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities

Project description:This SuperSeries is composed of the SubSeries listed below.

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