IDH-Mutated AML: Beyond Enasidenib and Ivosidenib Monotherapy: Highlights From SOHO 2021

Geppner, Alexis

doi:10.6004/jadpro.2022.13.1.11

JADPRO

2022

DOI: 10.6004/jadpro.2022.13.1.11

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IDH-Mutated AML: Beyond Enasidenib and Ivosidenib Monotherapy: Highlights From SOHO 2021

Alexis Geppner¹

Abstract: Alexis C. Geppner, MLS, CTTS, PA-C, of The University of Texas MD Anderson Cancer Center, distills information reviewed in the session on IDH-mutated acute myeloid leukemia presented by Courtney D. DiNardo, MD, MSCE, also of MD Anderson Cancer Center, at the 2021 SOHO Annual Meeting.

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2024

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Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia

Jang,

Koh,

Park

et al. 2024

IJMS

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Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from the bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, a higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to the reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating the acquisition of a rapid supply of ATP for proliferation in AML. Therefore, the targeting of mesothelin presents a potentially promising approach to mitigating the progression of AML through the inhibition of glycolysis and mitochondrial respiration in myeloid cells.

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Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia

Jang,

Koh,

Park

et al. 2024

IJMS

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show abstract

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IDH-Mutated AML: Beyond Enasidenib and Ivosidenib Monotherapy: Highlights From SOHO 2021

Abstract: Alexis C. Geppner, MLS, CTTS, PA-C, of The University of Texas MD Anderson Cancer Center, distills information reviewed in the session on IDH-mutated acute myeloid leukemia presented by Courtney D. DiNardo, MD, MSCE, also of MD Anderson Cancer Center, at the 2021 SOHO Annual Meeting.

Cited by 1 publication

References 7 publications

Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia

Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia

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