scholarly journals Targeting Metabolic Reprogramming in Acute Myeloid Leukemia

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 967 ◽  
Author(s):  
Isabel Castro ◽  
Belém Sampaio-Marques ◽  
Paula Ludovico
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Therapeutic Window ◽  
Tumor Proliferation ◽  
Preclinical Models ◽  
Promote Tumor Growth ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid

The cancer metabolic reprogramming allows the maintenance of tumor proliferation, expansion and survival by altering key bioenergetics, biosynthetic and redox functions to meet the higher demands of tumor cells. In addition, several metabolites are also needed to perform signaling functions that further promote tumor growth and progression. These metabolic alterations have been exploited in different cancers, including acute myeloid leukemia, as novel therapeutic strategies both in preclinical models and clinical trials. Here, we review the complexity of acute myeloid leukemia (AML) metabolism and discuss how therapies targeting different aspects of cellular metabolism have demonstrated efficacy and how they provide a therapeutic window that should be explored to target the metabolic requirements of AML cells.

Epitranscriptomic modifications in acute myeloid leukemia: m6A and 2′-O-methylation as targets for novel therapeutic strategies

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Cornelius Pauli ◽  
Michael Kienhöfer ◽  
Stefanie Göllner ◽  
Carsten Müller-Tidow
Keyword(s):  
Acute Myeloid Leukemia ◽  
Ribosomal Rna ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Rna Modifications ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid

Abstract Modifications of RNA commonly occur in all species. Multiple enzymes are involved as writers, erasers and readers of these modifications. Many RNA modifications or the respective enzymes are associated with human disease and especially cancer. Currently, the mechanisms how RNA modifications impact on a large number of intracellular processes are emerging and knowledge about the pathogenetic role of RNA modifications increases. In Acute Myeloid Leukemia (AML), the N 6-methyladenosine (m6A) modification has emerged as an important modulator of leukemogenesis. The writer proteins METTL3 and METTL14 are both involved in AML pathogenesis and might be suitable therapeutic targets. Recently, close links between 2′-O-methylation (2′-O-me) of ribosomal RNA and leukemogenesis were discovered. The AML1-ETO oncofusion protein which specifically occurs in a subset of AML was found to depend on induction of snoRNAs and 2′-O-me for leukemogenesis. Also, NPM1, an important tumor suppressor in AML, was associated with altered snoRNAs and 2′-O-me. These findings point toward novel pathogenetic mechanisms and potential therapeutic interventions. The current knowledge and the implications are the topic of this review.

scholarly journals Acute Myeloid Leukemia: Focus on novel Therapeutic Strategies

2012 ◽  
Vol 6 ◽  
pp. CMO.S7244 ◽  
Author(s):  
Tara L. Lin ◽  
M. Yair Levy
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Risk Groups ◽  
The Elderly ◽  
Therapeutic Strategies ◽  
Recent Advances ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid ◽  
Novel Therapeutic

Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly. Novel agents and treatment approaches are needed in the induction, post-remission and relapsed settings. The additions of clofarabine for relapsed or refractory disease and the hypomethylating agents represent recent advances. Clinical trials of FLT3 inhibitors have yielded disappointing results to date, with ongoing collaborations attempting to identify the optimal role for these agents. Potential leukemia stem cell targeted therapies and treatments in the setting of minimal residual disease are also under investigation. In this review, we will discuss recent advances in AML treatment and novel therapeutic strategies.

Abstract 1050: Efficacy of AMG 176 in combination with gilteritinib in preclinical models of acute myeloid leukemia

2021 ◽  
Author(s):  
Xiaoyue Chen ◽  
Sean Caenepeel ◽  
Brian Belmontes ◽  
Patricia L. McElroy ◽  
Karen Rex ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Preclinical Models ◽  
Acute Myeloid

scholarly journals Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia

2018 ◽  
Vol 19 (11) ◽  
pp. 3325 ◽  
Author(s):  
Lucille Stuani ◽  
Fabien Riols ◽  
Pierre Millard ◽  
Marie Sabatier ◽  
Aurélie Batut ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Acute Myeloid Leukemia ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Myeloid Leukemia ◽  
Metabolic Reprogramming ◽  
Frequent Relapses ◽  
The Impact ◽  
Mutant Cells ◽  
Acute Myeloid

Background: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one of the rare malignant hemopathies the therapy of which has not significantly improved during the past 30 years despite intense research efforts. One promising approach is to determine metabolic dependencies in AML cells. Moreover, two key metabolic enzymes, isocitrate dehydrogenases (IDH1/2), are mutated in more than 15% of AML patient, reinforcing the interest in studying metabolic reprogramming, in particular in this subgroup of patients. Methods: Using a multi-omics approach combining proteomics, lipidomics, and isotopic profiling of [U-13C] glucose and [U-13C] glutamine cultures with more classical biochemical analyses, we studied the impact of the IDH1 R132H mutation in AML cells on lipid biosynthesis. Results: Global proteomic and lipidomic approaches showed a dysregulation of lipid metabolism, especially an increase of phosphatidylinositol, sphingolipids (especially few species of ceramide, sphingosine, and sphinganine), free cholesterol and monounsaturated fatty acids in IDH1 mutant cells. Isotopic profiling of fatty acids revealed that higher lipid anabolism in IDH1 mutant cells corroborated with an increase in lipogenesis fluxes. Conclusions: This integrative approach was efficient to gain insight into metabolism and dynamics of lipid species in leukemic cells. Therefore, we have determined that lipid anabolism is strongly reprogrammed in IDH1 mutant AML cells with a crucial dysregulation of fatty acid metabolism and fluxes, both being mediated by 2-HG (2-Hydroxyglutarate) production.

scholarly journals Acute myeloid leukemia cells require 6-phosphogluconate dehydrogenase for cell growth and NADPH-dependent metabolic reprogramming

Oncotarget ◽  
2017 ◽  
Vol 8 (40) ◽  
pp. 67639-67650 ◽  
Author(s):  
Haymanti Bhanot ◽  
Ellen L. Weisberg ◽  
Mamatha M. Reddy ◽  
Atsushi Nonami ◽  
Donna Neuberg ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Growth ◽  
Myeloid Leukemia ◽  
Metabolic Reprogramming ◽  
Leukemia Cells ◽  
Phosphogluconate Dehydrogenase ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid
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