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Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shOPA1]

ABSTRACT: Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shOPA1]

PROVIDER: PRJNA918401 | ENA |

REPOSITORIES: ENA

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Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shOPA1]

Project description:Mitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial structure through the inhibition of mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-derived xenograft (PDX) models. Genetic depletion of mitofusin 2 (MFN2) or optic atrophy 1 (OPA1) or pharmacological inhibition of OPA1 (MYLS22) blocked mitochondrial fusion and had significant anti-leukemic activity, while having limited impact on normal hematopoietic cells ex vivo and in vivo. Mechanistically, inhibition of mitochondrial fusion disrupted mitochondrial respiration and reactive oxygen species production, leading to cell cycle arrest at the G0/G1 transition. These results nominate the inhibition of mitochondrial fusion as a promising therapeutic approach for AML.

2023-03-16 | GSE222168 | GEO

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shMFN2]

2023-03-16 | GSE222167 | GEO

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shMFN2]

Project description:Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX shMFN2]

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Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX MFN2 OE]

2023-03-16 | GSE222166 | GEO

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX MFN2 OE]

Project description:Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [PDX MFN2 OE]

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Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [Cell lines shCTL shMFN2]

2023-03-16 | GSE222165 | GEO

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia.

Project description:Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia.

| PRJNA918400 | ENA

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [Cell lines shCTL shMFN2]

Project description:Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia [Cell lines shCTL shMFN2]

| PRJNA918404 | ENA

Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia.

Project description:Mitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-derived xenograft (PDX) models. Genetic depletion of mitofusin 2 (MFN2) or optic atrophy 1 (OPA1) or pharmacological inhibition of OPA1 (MYLS22) blocked mitochondrial fusion and had significant anti-leukemic activity, while having limited impact on normal hematopoietic cells ex vivo and in vivo. Mechanistically, inhibition of mitochondrial fusion disrupted mitochondrial respiration and reactive oxygen species production, leading to cell cycle arrest at the G0/G1 transition. These results nominate the inhibition of mitochondrial fusion as a promising therapeutic approach for AML.

| S-EPMC10079528 | biostudies-literature

ATF4-Mediated Metabolic Stress Response as a Therapeutic Vulnerability in Chordoma [PDX RNA-seq]

Project description:ATF4-Mediated Metabolic Stress Response as a Therapeutic Vulnerability in Chordoma [PDX RNA-seq]

| PRJNA1152352 | ENA