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Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes (MDS)

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE116100 | GEO | 2018/08/01

REPOSITORIES: GEO

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Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes (MDS) [drug]

Project description:In this study we report that during evolution of MDS malignant HSCs activate distinct cellular programs that render such cells susceptible to therapeutic intervention. Specifically, metabolic analyses of the MDS stem cell compartment shows a profound activation of protein synthesis machinery and increased oxidative phosphorylation that occurs during later stages of MDS pathogenesis. Reliance on protein synthesis makes MDS stem cells senstive to translation inhibitors including homoharringtonine.

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Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes (MDS) [cell population]

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Project description:Myelodysplastic syndrome (MDS) is a chronic hematologic disorder that frequently evolves to more aggressive stages and in some cases leads to acute myeloid leukemia (AML). MDS arises from mutations in hematopoietic stem cells (HSCs). Thus, to define optimal therapies, it is essential to understand molecular events driving HSC pathogenesis. In this study, we report that during evolution of MDS, malignant HSCs activate distinct cellular programs that render such cells susceptible to therapeutic intervention. Specifically, metabolic analyses of the MDS stem cell compartment show a profound activation of protein synthesis machinery and increased oxidative phosphorylation. Pharmacological targeting of protein synthesis and oxidative phosphorylation demonstrated potent and selective eradication of MDS stem cells in primary human patient specimens. Taken together, our findings indicate that MDS stem cells are reliant on specific metabolic events and that such properties can be targeted prior to the onset of clinically significant AML, during antecedent MDS.

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Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes (MDS)

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Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes (MDS) [drug]

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Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes (MDS) [cell population]

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Emerging immuno-oncology targets in Myelodysplastic Syndromes (MDS).

Project description:Approaches to immunologic therapies in myelodysplastic syndromes (MDS) have generally fallen into 2 categories: therapies that target immune effector cells and enhance or direct an antileukemic effect, and therapies which target immunological markers on MDS progenitors themselves. Examples of the former include immune checkpoint inhibitors, immunomodulatory therapies, and vaccines, among others, while examples of the latter include antibody-drug conjugate therapies and naked antibodies; while bispecific antibodies and modified T-cells (such as CAR-T therapies) bridge both therapeutic modalities. In this review, we will discuss the rationale for the above therapies, clinical results to date, and potential future directions for investigation.

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Whole genome SNP array data from myelodysplastic syndromes (MDS) patients

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