Precision medicine for TP53-mutated acute myeloid leukemia

Brattås, Marte Karen; Reikvam, Håkon; Tvedt, Tor Henrik Anderson; Bruserud, Øystein

doi:10.1080/23808993.2019.1644164

Cited by 2 publications

(2 citation statements)

References 119 publications

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“…The metabolic status of AML cells can also be influenced by the amount of nutrients and metabolites in their microenvironment [9,10,46,60]. Modulation of systemic metabolic profiles may therefore be a strategy that indirectly affects the AML cells through alteration of their microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…Modulation of systemic metabolic profiles may therefore be a strategy that indirectly affects the AML cells through alteration of their microenvironment. Possible strategies could then be treatment with metformin and statins [60,61]. However, another alternative could be treatment with valproic acid that alters metabolic profiles, especially levels of several lipids/fatty acids and amino acid metabolites [62].…”

Section: Discussionmentioning

confidence: 99%

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Targeting Cellular Metabolism in Acute Myeloid Leukemia and the Role of Patient Heterogeneity

Grønningsæter

Reikvam

Aasebø

et al. 2020

Cells

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Acute myeloid leukemia (AML) is an aggressive blood cancer resulting in accumulation of immature, dysfunctional blood cells in the bone marrow. Changes in cell metabolism are features of many cancers, including AML and this may be exploited as a therapeutic target. In this study we investigated the in vitro antileukemic effects of seven metabolic inhibitors that target different metabolic pathways. The metabolic inhibitors were tested on AML cells derived from 81 patients using proliferation and viability assays; we also compared global gene expression and proteomic profiles for various patient subsets. Metformin, 2DG, 6AN, BPTES and ST1326 had strong antiproliferative and proapoptotic effects for most patients, whereas lonidamine and AZD3965 had an effect only for a minority. Antiproliferative effects on AML cells were additive when combined with the chemotherapeutic agent AraC. Using unsupervised hierarchical clustering, we identified a strong antiproliferative effect on AML cells after treatment with metabolic inhibitors for a subset of 29 patients. Gene expression and proteomic studies suggested that this subset was characterized by altered metabolic and transcriptional regulation. In addition, the Bcl-2 inhibitor venetoclax, in combination with 2DG or 6AN, increased the antiproliferative effects of these metabolic inhibitors on AML cells. Therapeutic targeting of cellular metabolism may have potential in AML, but the optimal strategy will likely differ between patients.

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Section: Discussionmentioning

confidence: 99%