<i>TET2</i> expression is a potential prognostic and predictive biomarker in cytogenetically normal acute myeloid leukemia

Zhang, Ting‐Juan; Zhou, Jing‐Dong; Yang, D L; Wang, Yuxin; Wen, Xiang‐mei; Guo, Hong; Yang, Lei; Lian, Xin‐Yue; Jiang, Lin; Qian, Jun

doi:10.1002/jcp.26373

Cited by 23 publications

(22 citation statements)

References 41 publications

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“…Decreased expression of TET2 was involved in prostate cancer progression by regulating global methylation status . Decreased expression levels of TET2 and 5‐hmC involving in the pathogenesis predicted adverse survival outcomes in AML and MDS . Experiments on two different mouse models have shown that TET2 deficiency affects the development of bone marrow and lymphoid lineage cells.…”

Section: Discussionmentioning

confidence: 99%

“…21 Decreased expression levels of TET2 and 5-hmC involving in the pathogenesis predicted adverse survival outcomes in AML and MDS. 9,14 Experiments on two different mouse models have shown that TET2 deficiency affects the development of bone marrow and lymphoid lineage cells. It is suggested that the injury of TET2 function or expression can also lead to the occurrence of hemolymphatic tumor.…”

Section: Discussionmentioning

confidence: 99%

“…Each sample was detected in triplicates. The relative mRNA level of TET2 to GAPDH gene was determined by the comparative cycle threshold (CT) method, which was described in literature . The cycle number difference (△CT = GAPDH ‐ TET2 ) was calculated for each triplicate and was expressed as 2 μ(△CT) .…”

Section: Methodsmentioning

confidence: 99%

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Low expression of TET2 gene in pediatric acute lymphoblastic leukemia is associated with poor clinical outcome

Zhang

Weng

Chen

et al. 2019

Int J Lab Hematology

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Introduction TET2, a member of the Ten‐Eleven translocation gene family, catalyzes the conversion of 5‐methylcytosine to 5‐hydroxymethylcytosine in DNA. Low expression of TET2 has been reported as a prognostic factor for several types of malignancies in adult patients. However, there have been few data on the effect of TET2 mRNA level on the prognosis of children with ALL so far. Methods In this study, TET2 expression of samples cryopreserved in the liquid nitrogen from January 1, 2007 through December 31, 2011 was retrospectively analyzed in 136 newly diagnosed ALL patients by real‐time polymerase chain reaction (PCR) assay. The patients' samples were divided into two groups by the median value of patients group and divided into TET2 low and TET2 high groups. Results A total of 136 childhood ALL patients demonstrated lower TET2 expression than control group (P = .038). TET2 mRNA expression levels were correlated with the disease status. In addition, patients with low TET2 expression had lower platelet counts and lower CR rates. Survival analysis showed that low TET2 expression in children with ALL was associated with lower 5‐year overall survival (OS) (63% vs 88%, P = .011) and event‐free survival (EFS) (60% vs 85%, P = .003). Multivariate analysis revealed that low TET2 expression was an independent poor prognostic factor of OS and EFS. Conclusion Low expression of TET2 in children with ALL is associated with poor prognosis and can be used as a molecular prognostic marker for risk group stratification.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Low expression of TET2 gene in pediatric acute lymphoblastic leukemia is associated with poor clinical outcome

Zhang

Weng

Chen

et al. 2019

Int J Lab Hematology

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“…Indeed TET2 expression and 5-hmC levels were found also decreased in pediatric MDS cases, a population known to be rarely mutated in TET2 gene [41]. TET2 expression levels have also been identified as a predictive and a prognostic biomarker in cytogenetically normal (CN)-AML [42]. Indeed, low TET2 expression had a negative impact on overall survival (OS) in both non-M3 and CN-AML (p = 0.016 and 0.044, respectively), although multivariable analysis confirmed these results only for the CN group [42].…”

Section: Tet2: a Pivotal Gene In Myeloid Malignanciesmentioning

confidence: 99%

The Interactome between Metabolism and Gene Mutations in Myeloid Malignancies

Gurnari

Pagliuca

Visconte

2021

IJMS

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The study of metabolic deregulation in myeloid malignancies has led to the investigation of metabolic-targeted therapies considering that cells undergoing leukemic transformation have excessive energy demands for growth and proliferation. However, the most difficult challenge in agents targeting metabolism is to determine a window of therapeutic opportunities between normal and neoplastic cells, considering that all or most of the metabolic pathways important for cancer ontogeny may also regulate physiological cell functions. Targeted therapies have used the properties of leukemic cells to produce altered metabolic products when mutated. This is the case of IDH1/2 mutations generating the abnormal conversion of α-ketoglutarate (KG) to 2-hydroxyglutarate, an oncometabolite inhibiting KG-dependent enzymes, such as the TET family of genes (pivotal in characterizing leukemia cells either by mutations, e.g., TET2, or by altered expression, e.g., TET1/2/3). Additional observations derive from the high sensitivity of leukemic cells to oxidative phosphorylation and its amelioration using BCL-2 inhibitors (Venetoclax) or by disrupting the mitochondrial respiration. More recently, nicotinamide metabolism has been described to mediate resistance to Venetoclax in patients with acute myeloid leukemia. Herein, we will provide an overview of the latest research on the link between metabolic pathways interactome and leukemogenesis with a comprehensive analysis of the metabolic consequences of driver genetic lesions and exemplificative druggable pathways.

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“…TET2 mutations are associated with an increased risk of MDS progression and confer a poor prognosis in AML [13,119]. Low TET2 mRNA levels are related to poor prognosis and TET2 mRNA levels might be a potential prognostic biomarker for AML since levels increase upon remission and decrease upon relapse [122].…”

Section: Epigenetic Changes In Age-related Haematopoietic Malignanmentioning

confidence: 99%

Epigenetic Changes as a Target in Aging Haematopoietic Stem Cells and Age-Related Malignancies

Buisman

Haan

2019

Cells

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Aging is associated with multiple molecular and functional changes in haematopoietic cells. Most notably, the self-renewal and differentiation potential of hematopoietic stem cells (HSCs) are compromised, resulting in myeloid skewing, reduced output of red blood cells and decreased generation of immune cells. These changes result in anaemia, increased susceptibility for infections and higher prevalence of haematopoietic malignancies. In HSCs, age-associated global epigenetic changes have been identified. These epigenetic alterations in aged HSCs can occur randomly (epigenetic drift) or are the result of somatic mutations in genes encoding for epigenetic proteins. Mutations in loci that encode epigenetic modifiers occur frequently in patients with haematological malignancies, but also in healthy elderly individuals at risk to develop these. It may be possible to pharmacologically intervene in the aberrant epigenetic program of derailed HSCs to enforce normal haematopoiesis or treat age-related haematopoietic diseases. Over the past decade our molecular understanding of epigenetic regulation has rapidly increased and drugs targeting epigenetic modifications are increasingly part of treatment protocols. The reversibility of epigenetic modifications renders these targets for novel therapeutics. In this review we provide an overview of epigenetic changes that occur in aging HSCs and age-related malignancies and discuss related epigenetic drugs.

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TET2 expression is a potential prognostic and predictive biomarker in cytogenetically normal acute myeloid leukemia

Cited by 23 publications

References 41 publications

Low expression of TET2 gene in pediatric acute lymphoblastic leukemia is associated with poor clinical outcome

Low expression of TET2 gene in pediatric acute lymphoblastic leukemia is associated with poor clinical outcome

The Interactome between Metabolism and Gene Mutations in Myeloid Malignancies

Epigenetic Changes as a Target in Aging Haematopoietic Stem Cells and Age-Related Malignancies

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