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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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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.

2023-08-04 | GSE208158 | GEO

Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities

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

| PRJNA858695 | ENA

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

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

| PRJNA858762 | ENA

Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities [DSP798]

Project description:Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities [DSP798]

| PRJNA858487 | ENA

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

2023-08-04 | GSE208186 | GEO

Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities [DSP798]

2023-08-04 | GSE208157 | GEO

CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia is sensitive to BCL-XL inhibition by navitoclax and DT2216

Project description:We engineered human models of CBFA2T3::GLIS2 acute megakaryoblastic leukemia and compared gene expression profiles to primary pediatric samples.

2023-09-22 | GSE209628 | GEO

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

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

2012-11-20 | E-GEOD-35203 | biostudies-arrayexpress

Mouse Models of Pediatric Acute Megakaryoblastic Leukemia Reveal Novel Therapeutic Vulnerabilities

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

2023-08-03 | GSE208187 | GEO

Whole Genome Sequencing of Pediatric Acute Megakaryoblastic Leukemia

Project description:<p>We have performed whole genome sequencing of 4 cases of pediatric acute megakaryoblastic leukemia to identify somatic genetic alterations driving leukemogenesis.</p>

| phs000413.v1.p1 | EGA

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