Improving prediction accuracy in acute myeloid leukaemia: micro-environment, immune and metabolic models

Hu, Fang; Wang, Yun; Wang, Weida; Gale, Robert Peter; Wu, Bingyi; Liang, Yang

doi:10.1038/s41375-021-01377-0

Cited by 5 publications

(5 citation statements)

References 47 publications

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“…Our results found that the high-risk group exhibited lower ESTIMATE and immune score than the low-risk group. The immune micro-environment is constructed by tumor cells and tumor in ltrating immune cells, which regulate the expression pattern of immune checkpoints [17]. Consistent with the immune score result, PD1 signaling and immune response were enriched in the low-risk group.…”

Section: Discussionmentioning

confidence: 54%

A 4-lethal gene prognostic signature correlates with genomic instability and immunotherapy biomarker in stomach adenocarcinoma

Fei

2022

Preprint

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The lethal genes manifesting significant prognostic value have not been systematically explored in stomach adenocarcinoma (STAD). The current study aims at evaluating the cell viability-related lethal genes by examining the results of CRISPR-cas9 screening, in an attempt to reveal novel therapeutic targets for STAD. Patient data were gathered from The Cancer Genome Atlas (TCGA), and the lethal genes were identified by conducting genome-scale CRISPR screening of the RNA sequencing data from DepMap. A few genes were selected from STAD lineage preferential dependency candidates derived from DepMap for investigation of genomic alterations, survival outcomes, immune profiles and signaling activities. After narrowing down the processes, four lethal genes were sorted out to construct a risk signature that proves to be a novel and independent prognostic factor. The enrolled patients were subdivided into a low-risk group and a high-risk group in accordance with the risk score. Gene set enrichment analysis demonstrated that certain cancer-related phenotypes were significantly enriched in the high-risk group. Patients in the high-risk group exhibited a low immune score, higher aneuploidy and down-regulated level of PD1 than the low-risk group.In conclusion, our study of CRISPR-cas9 Screening constructed a robust four-lethal gene prognostic signature, which could be applied as a useful prognostic biomarker and thereby highlighting the potential therapeutic targets for the intervention of STAD.

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Section: Discussionmentioning

confidence: 54%

A 4-lethal gene prognostic signature correlates with genomic instability and immunotherapy biomarker in stomach adenocarcinoma

Fei

2022

Preprint

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“…However, most of these studies do not account for major cofounding factors (such as treatment type and stem cell transplantation) or do not contain a validation cohort. When performed, well‐made studies using validation cohorts hardly reach a concordance statistic of 0.8, most of them being around 0.7 64,65 . More recently, Vadakekolathu J. et al proposed an immune score based on IFN‐γ‐related genes that was able to predict response to flotetuzumab (a CD3xCD123 bispecific antibody) with an AUC of 0.84 22 .…”

Section: Discussionmentioning

confidence: 99%

“…When performed, well-made studies using validation cohorts hardly reach a concordance statistic of 0.8, most of them being around 0.7. 64,65 More recently, Vadakekolathu J. et al proposed an immune score based on IFN-γ-related genes that was able to predict response to flotetuzumab (a CD3xCD123 bispecific antibody) with an AUC of 0.84. 22 Our results suggest that the systematic association of HERVs with gene expression could greatly improve gene expression-based predictors.…”

Section: Discussionmentioning

confidence: 99%

HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy

et al. 2022

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Human endogenous retroviruses (HERVs) represent 8% of the human genome. The expression of HERVs and their immune impact have not been extensively studied in Acute Myeloid Leukemia (AML). In this study, we used a reference of 14 968 HERV functional units to provide a thorough analysis of HERV expression in normal and AML bone marrow cells. We show that the HERV retrotranscriptome accurately characterizes normal and leukemic cell subpopulations, including leukemia stem cells, in line with different epigenetic profiles. We then show that HERV expression delineates AML subtypes with different prognoses. We finally propose a method to select and prioritize CD8+ T cell epitopes derived from AML‐specific HERVs and we show that lymphocytes infiltrating patient bone marrow at diagnosis contain naturally occurring CD8+ T cells against these HERV epitopes. We also provide in vitro data supporting the functionality of HERV‐specific CD8+ T‐cells against AML cells. These results show that HERVs represent an important source of genetic information that can help enhancing disease stratification or biomarker identification and an important reservoir of alternative tumor‐specific T cell epitopes relevant for cancer immunotherapy.

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“…In addition, serum metabolomic analysis has been used to identify metabolites associated with the outcome of children with AML receiving chemotherapy (50,51).…”

Section: Potential Clinical Application Of Metabolic Reprogramming 1 ...mentioning

confidence: 99%

“… 49 ). In addition, serum metabolomic analysis has been used to identify metabolites associated with the outcome of children with AML receiving chemotherapy ( 50, 51 ). According to a recent urine metabolomics study of patients with non–Hodgkin lymphoma (NHL; 15 samples), 18 metabolites were detected by gas chromatography–mass spectroscopy (GC-MS) and gave a satisfying diagnostic value with an area under the ROC > 0.998 ( 52 ).…”

Section: Potential Clinical Application Of Metabolic Reprogrammingmentioning

confidence: 99%

Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives

Wang

Zhou

2022

Cancer Research

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Metabolic reprogramming is a hallmark of cancer progression. Metabolic activity supports tumorigenesis and tumor progression, allowing cells to uptake essential nutrients from the environment and use the nutrients to maintain viability and support proliferation. The metabolic pathways of malignant cells are altered to accommodate increased demand for energy, reducing equivalents, and biosynthetic precursors. Activated oncogenes coordinate with altered metabolism to control cell-autonomous pathways, which can lead to tumorigenesis when abnormalities accumulate. Clinical and preclinical studies have shown that targeting metabolic features of hematological malignancies is an appealing therapeutic approach. This review provides a comprehensive overview of the mechanisms of metabolic reprogramming in hematologic malignancies and potential therapeutic strategies to target cancer metabolism.

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Improving prediction accuracy in acute myeloid leukaemia: micro-environment, immune and metabolic models

Cited by 5 publications

References 47 publications

A 4-lethal gene prognostic signature correlates with genomic instability and immunotherapy biomarker in stomach adenocarcinoma

A 4-lethal gene prognostic signature correlates with genomic instability and immunotherapy biomarker in stomach adenocarcinoma

HERVs characterize normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy

Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives

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