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Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML.

ABSTRACT: Acute myeloid leukemia (AML) is a devastating cancer affecting the hematopoietic system. Previous research has relied on RNA sequencing and microarray techniques to study the downstream effects of genomic alterations. While these studies have proven efficacious, they fail to capture the changes that occur at the proteomic level. To interrogate the effect of protein expression alterations in AML, we performed a quantitative mass spectrometry in parallel with RNAseq analysis using AML mouse models. These combined results identified 34 proteins whose expression was upregulated in AML tumors, but strikingly, were unaltered at the transcriptional level. Here we focus on mitochondrial electron transfer proteins ETFA and ETFB. Silencing of ETFA and ETFB led to increased mitochondrial activity, mitochondrial stress, and apoptosis in AML cells, but had little to no effect on normal human CD34⁺ cells. These studies identify a set of proteins that have not previously been associated with leukemia and may ultimately serve as potential targets for therapeutic manipulation to hinder AML progression and help contribute to our understanding of the disease.

SUBMITTER: Caplan M

PROVIDER: S-EPMC9061297 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML.

Caplan Mika M Wittorf Karli J KJ Weber Kasidy K KK Swenson Samantha A SA Gilbreath Tyler J TJ Willow Hynes-Smith R R Amador Catalina C Hyde R Katherine RK Buckley Shannon M SM

Leukemia 20220217 5

Acute myeloid leukemia (AML) is a devastating cancer affecting the hematopoietic system. Previous research has relied on RNA sequencing and microarray techniques to study the downstream effects of genomic alterations. While these studies have proven efficacious, they fail to capture the changes that occur at the proteomic level. To interrogate the effect of protein expression alterations in AML, we performed a quantitative mass spectrometry in parallel with RNAseq analysis using AML mouse models ...[more]

PMID: 35177813

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Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML.

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Multi-omics reveals mitochondrial metabolism proteins susceptible for drug discovery in AML.

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