Patterns of mutations in TP53 mutated AML

Welch, John S.

doi:10.1016/j.beha.2018.09.010

Cited by 39 publications

(26 citation statements)

References 59 publications

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“…NF-κB and TCR were also significantly enriched according to the GSEA enrichment results. The p53 gene is critical for hematopoietic stem cell function and its dysfunction can affect the evolution, biological phenotype, treatment response, and prognosis of AML [ 28 – 31 ]. Evaluation of the function of p53 protein is conducive to accurate p53-based targeted therapy for AML [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of signal recognition particle 14 as a prognostic biomarker predicting overall survival in patients with acute myeloid leukemia

2021

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Background This study aimed to determine and verify the prognostic value and potential functional mechanism of signal recognition particle 14 (SRP14) in acute myeloid leukemia (AML) using a genome-wide expression profile dataset. Methods We obtained an AML genome-wide expression profile dataset and clinical prognostic data from The Cancer Genome Atlas (TCGA) and GSE12417 databases, and explored the prognostic value and functional mechanism of SRP14 in AML using survival analysis and various online tools. Results Survival analysis showed that AML patients with high SRP14 expression had poorer overall survival than patients with low SRP14 expression. Time-dependent receiver operating characteristic curves indicated that SRP14 had good accuracy for predicting the prognosis in patients with AML. Genome-wide co-expression analysis suggested that SRP14 may play a role in AML by participating in the regulation of biological processes and signaling pathways, such as cell cycle, cell adhesion, mitogen-activated protein kinase, tumor necrosis factor, T cell receptor, DNA damage response, and nuclear factor-kappa B (NF-κB) signaling. Gene set enrichment analysis indicated that SRP14 was significantly enriched in biological processes and signaling pathways including regulation of hematopoietic progenitor cell differentiation and stem cell differentiation, intrinsic apoptotic signaling pathway by p53 class mediator, interleukin-1, T cell mediated cytotoxicity, and NF-κB-inducing kinase/NF-κB signaling. Using the TCGA AML dataset, we also identified four drugs (phenazone, benzydamine, cinnarizine, antazoline) that may serve as SRP14-targeted drugs in AML. Conclusion The current results revealed that high SRP14 expression was significantly related to a poor prognosis and may serve as a prognostic biomarker in patients with AML.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of signal recognition particle 14 as a prognostic biomarker predicting overall survival in patients with acute myeloid leukemia

2021

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“…A variety of genes, such as HOXA9, MEIS1 and TP53, have been shown to be critically involved in AML pathogenesis (23)(24)(25)(26). The upregulation of HOXA9 was reported in more than 50% of AML and is highly associated with poor prognosis (23).…”

Section: The Level Of Bdh1 Is Significantly Correlated With Hoxa9 Meis1 and Tp53 Expression Levelsmentioning

confidence: 99%

“…The combinational overexpression of Hoxa9 and Meis1 leads to a massive acceleration of leukemia development (25). As a tumor suppressor gene, TP53 inactivation by gene deletion or mutation potently promotes AML (26) (Figure 4A). We found that cell viability of MA9 BM cells overexpressing Bdh1 was significantly lower than control group (Figure 4B).…”

Section: The Level Of Bdh1 Is Significantly Correlated With Hoxa9 Meis1 and Tp53 Expression Levelsmentioning

confidence: 99%

Anti-Tumor Effects of BDH1 in Acute Myeloid Leukemia

et al. 2021

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Dysregulation of ketone metabolism has been reported in various types of cancer. In order to find out its role in acute myeloid leukemia (AML) pathogenesis, we first analyzed the expression levels of 10 key genes involved in ketone metabolism in AML blasts and CD34+ hematopoietic stem cells (HSCs) from healthy donors. We found that the expression level of BDH1 was significantly lower in AML than in normal HSCs. The downregulation of BDH1 gene expression in AML cell lines as compared with normal HSCs was further confirmed with real-time RT-PCR. Analysis of TCGA and other database revealed that the downregulation of BDH1 was associated with worse prognosis in AML patients. In addition, we showed that overexpression of BDH1 inhibited the viability and proliferation of AML cells. In contrast, BDH1 knock-down promoted AML cell growth. Collectively, our results suggest the previously unappreciated anti-tumor role of BDH1 in AML, and low BDH1 expression predicts poor survival.

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“…Usually, TP53 -mutated MNs are not characterized by single nucleotide variants only, but the mechanism of clonal progression to t-MN likely involves copy number alterations and the acquisition of other mutations [ 60 ]. Deeper sequencing of CHIP mutations within TP53 -mutated samples demonstrated sub-clonal chromosome 5 and 7 copy number variations many years before the diagnosis of t-MN, suggesting that TP53 clones precede the development of cytogenetic abnormalities in t-MN.…”

Section: The Case Of Tp53 and Ppm1d In Therapy-related Chipmentioning

confidence: 99%

From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression

Gurnari

Fabiani

Falconi

et al. 2021

Biology

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Clonal hematopoiesis (CH) has been recognized as a predisposing factor for the development of myeloid malignancies. Its detection has been reported at different frequencies across studies, based on the type of genome scanning approach used and the population studied, but the latest insights recognize its virtual ubiquitous presence in older individuals. The discovery of CH in recent years paved the way for a shift in the paradigm of our understanding of the biology of therapy-related myeloid malignancies (t-MNs). Indeed, we moved from the concept of a treatment-induced lesion to a model where CH precedes the commencement of any cancer-related treatment in patients who subsequently develop a t-MN. Invariant patterns of genes seem to contribute to the arising of t-MN cases, with differences regarding the type of treatment received. Here, we review the principal studies concerning CH, the relationship with myeloid progression and the mechanisms of secondary t-MN development.

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Patterns of mutations in TP53 mutated AML

Cited by 39 publications

References 59 publications

Identification and validation of signal recognition particle 14 as a prognostic biomarker predicting overall survival in patients with acute myeloid leukemia

Identification and validation of signal recognition particle 14 as a prognostic biomarker predicting overall survival in patients with acute myeloid leukemia

Anti-Tumor Effects of BDH1 in Acute Myeloid Leukemia

From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression

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