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Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE252746 | GEO | 2024/02/01

REPOSITORIES: GEO

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Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).

Project description:Germline, mono-allelic mutations in RUNX1 cause familial platelet disorder (RUNX1-FPD) that evolves into myeloid malignancy (FPD-MM): MDS or AML. FPD-MM commonly harbors co-mutations in the second RUNX1 allele and/or other epigenetic regulators. Here we utilized patient-derived (PD) FPD-MM cells and established the first FPD-MM AML cell line (GMR-AML1). GMR-AML1 cells exhibited active super-enhancers of MYB, MYC, BCL2 and CDK6, augmented expressions of c-Myc, c-Myb, EVI1 and PLK1 and surface markers of AML stem cells. In longitudinally studied bone marrow cells from a patient at FPD-MM vs RUNX1-FPD state, we confirmed increased chromatin accessibility and mRNA expressions of MYB, MECOM and BCL2 in FPD-MM cells. GMR-AML1 and PD FPD-MM cells were sensitive to homoharringtonine (HHT or omacetaxine) or mebendazole-induced lethality, associated with repression of c-Myc, EVI1, PLK1, CDK6 and MCL1. Co-treatment with MB and the PLK1 inhibitor volasertib exerted synergistic in vitro lethality in GMR-AML1 cells. In luciferase-expressing GMR-AML1 xenograft model, MB, omacetaxine or volasertib monotherapy, or co-treatment with MB and volasertib, significantly reduced AML burden and improved survival in the immune-depleted mice. These findings highlight the molecular features of FPD-MM progression and demonstrate HHT, MB and/or volasertib as effective agents against cellular models of FPD-MM.

| S-EPMC10844204 | biostudies-literature

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ChIP-Seq]

2024-02-01 | GSE252739 | GEO

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [scRNA-Seq]

2024-02-01 | GSE252745 | GEO

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ATAC-Seq]

2024-02-01 | GSE252743 | GEO

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [Stranded mRNA-Seq]

2024-02-01 | GSE252740 | GEO

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).

| PRJNA1062371 | ENA

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [scRNA-Seq]

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [scRNA-Seq]

| PRJNA1062378 | ENA

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ChIP-Seq]

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ChIP-Seq]

| PRJNA1062377 | ENA

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ATAC-Seq]

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [ATAC-Seq]

| PRJNA1062379 | ENA

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [Stranded mRNA-Seq]

Project description:Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). [Stranded mRNA-Seq]

| PRJNA1062376 | ENA

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