ORCID Profile
0000-0002-4789-3294
Current Organisation
Royal Brisbane and Women's Hospital
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Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.22541661.V1
Abstract: Supplementary Figure file showing Figures S1-S7
Publisher: American Association for Cancer Research (AACR)
Date: 10-11-2022
DOI: 10.1158/2159-8290.CD-21-0218
Abstract: Oncogenic mutations in both IDH1 and IDH2 produce 2-hydroxyglutarate and are generally considered equivalent in terms of pathogenesis and targeting. Using comprehensive metabolomic analysis, we demonstrate unexpected metabolic differences in fatty acid metabolism between mutant IDH1 and IDH2 in patient s les with targetable metabolic interventions. See related commentary by Robinson and Levine, p. 266. This article is highlighted in the In This Issue feature, p. 247
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.22541661
Abstract: Supplementary Figure file showing Figures S1-S7
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.C.6549714.V1
Abstract: Abstract Isocitrate dehydrogenase 1 and 2 (IDH) are mutated in multiple cancers and drive production of ( i R /i )-2-hydroxyglutarate (2HG). We identified a lipid synthesis enzyme [acetyl CoA carboxylase 1 (ACC1)] as a synthetic lethal target in mutant IDH1 (mIDH1), but not mIDH2, cancers. Here, we analyzed the metabolome of primary acute myeloid leukemia (AML) blasts and identified an mIDH1-specific reduction in fatty acids. mIDH1 also induced a switch to b-oxidation indicating reprogramming of metabolism toward a reliance on fatty acids. Compared with mIDH2, mIDH1 AML displayed depletion of NADPH with defective reductive carboxylation that was not rescued by the mIDH1-specific inhibitor ivosidenib. In xenograft models, a lipid-free diet markedly slowed the growth of mIDH1 AML, but not healthy CD34 sup + /sup hematopoietic stem rogenitor cells or mIDH2 AML. Genetic and pharmacologic targeting of ACC1 resulted in the growth inhibition of mIDH1 cancers not reversible by ivosidenib. Critically, the pharmacologic targeting of ACC1 improved the sensitivity of mIDH1 AML to venetoclax. Significance: Oncogenic mutations in both IDH1 and IDH2 produce 2-hydroxyglutarate and are generally considered equivalent in terms of pathogenesis and targeting. Using comprehensive metabolomic analysis, we demonstrate unexpected metabolic differences in fatty acid metabolism between mutant IDH1 and IDH2 in patient s les with targetable metabolic interventions. i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-22-1325" target="_blank" See related commentary by Robinson and Levine, p. 266 /a . /i i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-13-2-ITI" target="_blank" This article is highlighted in the In This Issue feature, p. 247 /a /i /
Publisher: Springer Science and Business Media LLC
Date: 29-05-2023
DOI: 10.1186/S12884-023-05714-2
Abstract: Although associations between maternal exposure to adverse childhood experiences (ACEs) and perinatal anxiety and depression are established, there is a paucity of information about the associations between ACEs and perinatal trauma and perinatal post-traumatic stress outcomes. For the purposes of this article, perinatal trauma is defined as a very frightening or distressing event that may result in psychological harm. The event must have been related to conception, pregnancy, birth, and up to 12 months postpartum. Women recruited at an antenatal appointment ( n = 262) were invited to complete online surveys at two-time points mid-pregnancy and eight weeks after the estimated date of delivery. The ACE Q 10-item self-reporting tool and a perinatal trauma screen related to the current and/or a previous perinatal period were completed. If the perinatal trauma screen was positive at either time point in the study, women were invited to complete a questionnaire examining symptoms of perinatal post-traumatic stress disorder and, if consenting, a clinical interview where the Post-traumatic Symptoms Scale was administered. Sixty women (22.9%) reported four or more ACEs. These women were almost four times more likely to endorse perinatal trauma, when compared with those who either did not report ACEs (OR = 3.6, CI 95% 1.74 – 7.36, p 0.001) or had less than four ACEs (OR = 3.9, CI 95% 2.037.55, p 0.001). A 6–sevenfold increase in perinatal trauma was seen amongst women who reported having at least one ACE related to abuse (OR = 6.23, CI 95% 3.32–11.63, p 0.001) or neglect (OR = 6.94, CI 95% 2.95–16.33, p 0.001). The severity of perinatal-PTSD symptoms for those with perinatal trauma in pregnancy was significantly higher in those women exposed to at least one ACE related to abuse. Awareness of maternal exposure to childhood adversity/maltreatment is critical to providing trauma-informed approaches in the perinatal setting. Our study suggests that routine screening for ACEs in pregnancy adds clinical value. This adds to previous research confirming the relationship between ACEs and mental health complexities and suggests that ACEs influence perinatal mental health outcomes.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.22541658
Abstract: Table S1 showing AML primary cell details for metabolomics
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.C.6549714
Abstract: Abstract Isocitrate dehydrogenase 1 and 2 (IDH) are mutated in multiple cancers and drive production of ( i R /i )-2-hydroxyglutarate (2HG). We identified a lipid synthesis enzyme [acetyl CoA carboxylase 1 (ACC1)] as a synthetic lethal target in mutant IDH1 (mIDH1), but not mIDH2, cancers. Here, we analyzed the metabolome of primary acute myeloid leukemia (AML) blasts and identified an mIDH1-specific reduction in fatty acids. mIDH1 also induced a switch to b-oxidation indicating reprogramming of metabolism toward a reliance on fatty acids. Compared with mIDH2, mIDH1 AML displayed depletion of NADPH with defective reductive carboxylation that was not rescued by the mIDH1-specific inhibitor ivosidenib. In xenograft models, a lipid-free diet markedly slowed the growth of mIDH1 AML, but not healthy CD34 sup + /sup hematopoietic stem rogenitor cells or mIDH2 AML. Genetic and pharmacologic targeting of ACC1 resulted in the growth inhibition of mIDH1 cancers not reversible by ivosidenib. Critically, the pharmacologic targeting of ACC1 improved the sensitivity of mIDH1 AML to venetoclax. Significance: Oncogenic mutations in both IDH1 and IDH2 produce 2-hydroxyglutarate and are generally considered equivalent in terms of pathogenesis and targeting. Using comprehensive metabolomic analysis, we demonstrate unexpected metabolic differences in fatty acid metabolism between mutant IDH1 and IDH2 in patient s les with targetable metabolic interventions. i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-22-1325" target="_blank" See related commentary by Robinson and Levine, p. 266 /a . /i i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-13-2-ITI" target="_blank" This article is highlighted in the In This Issue feature, p. 247 /a /i /
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2159-8290.22541658.V1
Abstract: Table S1 showing AML primary cell details for metabolomics
No related grants have been discovered for elizabeth bennett.