Mitochondrial dependency in progression of acute myeloid leukemia

Basak, Nandini Pal; Banerjee, Subrata

doi:10.1016/j.mito.2015.01.006

Cited by 62 publications

(63 citation statements)

References 109 publications

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“…Mitochondria is a key organelles in human cells participating in cell apoptosis [28, 29], and it also plays important roles in AML progress and chemosensitivity [30]. Energy is greatly demanded in cancer cells, therefore, more adenosine triphosphate (ATP) synthesized by mitochondrion is required.…”

Section: Discussionmentioning

confidence: 99%

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia

et al. 2016

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The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10−4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis.

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Section: Discussionmentioning

confidence: 99%

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia

et al. 2016

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“…Multiple reports have suggested that despite enhanced glycolysis, cancer cells can produce a significant fraction of their ATP via mitochondrial respiration (Caino et al, 2015; LeBleu et al, 2014; Lu et al, 2015; Maiuri and Kroemer, 2015; Tan et al, 2015; Viale et al, 2015; Ward and Thompson, 2012; Xu et al, 2015). In a growing tumor, adaptive metabolic reprogramming, precipitated in part by oncogenic transformation, gives cancer cells the advantage of active proliferation, functional motility, and metastasis (Basak and Banerjee, 2015; Caino et al, 2015; LeBleu et al, 2014). A recent study by Tan et al has described that when mitochondrial DNA (mtDNA)-depleted tumor cells (ρ 0 cells) were injected into mice, they enhanced their tumor growth property by acquisition of mtDNA from the host mouse cells and reassembling a mitochondrial electron transport chain complex (ETC) and respiratory function (Tan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer

et al. 2016

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Summary Transmitochondrial cybrids and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in triple negative breast cancer (TNBC). Analysis of cybrids and established breast cancer (BC) cell lines showed that metastatic TNBC maintains high levels of ATP through fatty acid β-oxidation (FAO) and activates Src oncoprotein through autophosphorylation at Y419. Manipulation of FAO including the knocking down of carnitine palmitoyltransferase-1 (CPT1) and 2 (CPT2), the rate-limiting proteins of FAO, and analysis of patient-derived xenograft models, confirmed the role of mitochondrial FAO in Src activation and metastasis. Analysis of TCGA and other independent BC clinical data further reaffirmed the role of mitochondrial FAO and CPT genes in Src regulation and their significance in BC metastasis.

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“…IDH3 is an isoform of the IDH enzyme that catalyzes the conversion of isocitrate into alpha(α)-ketoglutarate in TCA cycle. The isoforms IDH1 and IDH2 catalyze the same reaction outside the TCA cycle [2]. Mutations in IDH1 confer inferior overall survival (OS) and higher risk of relapse in molecular low-risk AML patients with normal karyotype (mutated nucleophosmin (NPM1) without FLT3-ITD mutation), while single nucleotide polymorphism (SNP) rs11554137 is associated with inferior outcome in molecular high-risk AML patients with normal karyotype (mutated or wilt type NPM1 with FLT3-ITD mutation).…”

Section: Altered Mitochondrial Metabolism In Amlmentioning

confidence: 99%

“…IDH2 R172 mutation is associated with lower complete remission (CR) rate. Both IDH1 and IDH2 mutations confer an enzymatic gain of function that endows the enzyme with the ability to convert α-ketoglutarate into 2-hydroxyglutarate (2HG) [2,12]. 2HG is an oncometabolite associated with repression of the inducible expression of lineage-specific differentiation genes and a block to differentiation by impairing histone methylation [2,13].…”

Section: Altered Mitochondrial Metabolism In Amlmentioning

confidence: 99%

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Targeting the mitochondria in acute myeloid leukemia

Sánchez-Mendoza

Rego

2017

Appl Cancer Res

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Acute myeloid leukemia (AML) is a clonal hematologic neoplasm characterized by heterogeneity of genetic abnormalities found at diagnosis. These abnormalities serve to classify patients by risk group into low, intermediate, and high risk. It also provides specific targets for the development of new combinational therapies. However, because of the heterogeneity of genetic abnormalities, targeted therapy is not always possible. Altered mitochondrial metabolism is a common feature in cancer cells, a phenomenon first described by Otto Warburg. In AML patients, the discovery of mutations in the isocitrate dehydrogenase gene provided for the first time a link between altered mitochondrial metabolism and AML. This raised the possibility of testing drugs known as mitocans for new combinational therapeutic approaches. Mitocans are a diverse group of anti-cancer compounds that target mitochondria. They disrupt energy production leading to enhanced generation of reactive oxygen species along with the activation of the intrinsic pathway of apoptosis. The present review discusses the different types of mitocans and their mechanism of action along with preclinical and clinical studies in AML.

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Mitochondrial dependency in progression of acute myeloid leukemia

Cited by 62 publications

References 109 publications

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia

Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer

Targeting the mitochondria in acute myeloid leukemia

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