scholarly journals Screening the Cancer Genome Atlas Database for Genes of Prognostic Value in Acute Myeloid Leukemia

2020 ◽  
Vol 9 ◽  
Author(s):  
Jie Ni ◽  
Yang Wu ◽  
Feng Qi ◽  
Xiao Li ◽  
Shaorong Yu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas ◽  
Acute Myeloid

Molecular Markers of Regulatory T Cells in Cancer Immunotherapy with Special Focus on Acute Myeloid Leukemia (AML) - A Systematic Review

2020 ◽  
Vol 27 (28) ◽  
pp. 4673-4698 ◽  
Author(s):  
Parham Jabbarzadeh Kaboli ◽  
Lingling Zhang ◽  
Shixin Xiang ◽  
Jing Shen ◽  
Mingxing Li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Molecular Markers ◽  
Adverse Effects ◽  
Myeloid Leukemia ◽  
Treg Cells ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas ◽  
Acute Myeloid

The next-generation immunotherapy can only be effective if researchers have an in-depth understanding of the function and regulation of Treg cells in antitumor immunity combined with the discovery of new immunity targets. This can enhance clinical efficacy of future and novel therapies and reduces any adverse reactions arising from the latter. This review discusses tumor treatment strategies using regulatory T (Treg) cell therapy in a Tumor Microenvironment (TME). It also discusses factors affecting TME instability as well as relevant treatments to prevent future immune disorders. It is prognosticated that PD-1 inhibitors are risky and their adverse effects should be taken into account when they are administered to treat Acute Myeloid Leukemia (AML), lung adenocarcinoma, and prostate adenocarcinoma. In contrast, Treg molecular markers FoxP3 and CD25 analyzed here have stronger expression in almost all kinds of cancers compared with normal people. However, CD25 inhibitors are more effective compared to FoxP3 inhibitors, especially in combination with TGF-β blockade, in predicting patient survival. According to the data obtained from the Cancer Genome Atlas, we then concentrate on AML immunotherapy and discuss different therapeutic strategies including anti-CD25/IL-2, anti-CTLA-4, anti-IDO, antityrosine kinase receptor, and anti-PI3K therapies and highlight the recent advances and clinical achievements in AML immunotherapy. In order to prognosticate the risk and adverse effects of key target inhibitors (namely against CTLA-4, FoxP3, CD25, and PD-1), we finally analyzed and compared the Cancer Genome Atlas derived from ten common cancers. This review shows that Treg cells are strongly increased in AML and the comparative review of key markers shows that Tregbased immunotherapy is not effective for all kinds of cancer. Therefore, blocking CD25(+)FoxP3(+) Treg cells is suggested in AML more than other kinds of cancer; meanwhile, Treg markers studied in other cancers have also great lessons for AML immunotherapy.

scholarly journals A proteomic approach to understand the clinical significance of acute myeloid leukemia-derived extracellular vesicles reflecting essential characteristics of leukemia

2020 ◽  
pp. mcp.RA120.002169
Author(s):  
Ka-Won Kang ◽  
Hyoseon Kim ◽  
Woojune Hur ◽  
Jik-han Jung ◽  
Su Jin Jeong ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Extracellular Vesicle ◽  
The Cancer Genome Atlas ◽  
Enzyme Linked Immunosorbent Assay ◽  
Expression Levels ◽  
Proteomic Approach ◽  
Cancer Genome Atlas ◽  
Acute Myeloid

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. Enzyme-linked immunosorbent assay results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML-derived EVs could reflect essential leukemia biology.

scholarly journals Diagnosis and prognostic value of C-X-C motif chemokine ligand 1 in colon adenocarcinoma based on The Cancer Genome Atlas and Guangxi cohort

2021 ◽  
Vol 12 (18) ◽  
pp. 5506-5518
Author(s):  
Yi-Zhen Gong ◽  
Hui Ma ◽  
Guo-Tian Ruan ◽  
Li-Chen Zhu ◽  
Xi-Wen Liao ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Colon Adenocarcinoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Chemokine Ligand ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals High expression of AK1 predicts inferior prognosis in acute myeloid leukemia patients undergoing chemotherapy

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Tong Qin ◽  
Hongmian Zhao ◽  
Yunli Shao ◽  
Ning Hu ◽  
Jinlong Shi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
The Cancer Genome Atlas ◽  
Hematopoietic Stem ◽  
Expression Levels ◽  
Cancer Genome Atlas ◽  
Adenylate Kinase 1 ◽  
Acute Myeloid

Abstract The purpose of the present study was to investigate whether expression levels of adenylate kinase 1 (AK1) were associated with prognosis of acute myeloid leukemia (AML) in patients treated with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). 85 AML patients with AK1 expression report who received chemotherapy-alone and 71 who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either AK1high or AK1low based on their AK1 expression level relative to the median. Then, overall survival (OS) and event-free survival (EFS) were compared between patients with high vs. low AK1 expression. In the chemotherapy group, high AK1 expression was favorable for both EFS (P=0.016) and OS (P=0.014). In the allo-HSCT group, there was no association for AK1 expression levels and clinical outcomes. Further analyses suggested that in the high AK1 expression group, EFS and OS were longer in patients treated with allo-HSCT compared with those treated with chemotherapy (P=0.0011; P<0.0001, respectively), whereas no significant differences were observed in the low AK1 expression group. In summary, we reported AK1 as an independent unfavorable prognostic factor of AML patients undergoing chemotherapy, and its use could also facilitate clinical decision-making in selecting treatment for AML patients. Patients with high AK1 expression may be recommended for early allo-HSCT.

scholarly journals The hidden genomic landscape of acute myeloid leukemia: subclonal structure revealed by undetected mutations

Blood ◽  
2015 ◽  
Vol 125 (4) ◽  
pp. 600-605 ◽  
Author(s):  
Margherita Bodini ◽  
Chiara Ronchini ◽  
Luciano Giacò ◽  
Anna Russo ◽  
Giorgio E. M. Melloni ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Critical Evaluation ◽  
Variant Calling ◽  
High Specificity ◽  
The Cancer Genome Atlas ◽  
High Rate ◽  
Variant Allele ◽  
Cancer Genome Atlas ◽  
Acute Myeloid

Abstract The analyses carried out using 2 different bioinformatics pipelines (SomaticSniper and MuTect) on the same set of genomic data from 133 acute myeloid leukemia (AML) patients, sequenced inside the Cancer Genome Atlas project, gave discrepant results. We subsequently tested these 2 variant-calling pipelines on 20 leukemia samples from our series (19 primary AMLs and 1 secondary AML). By validating many of the predicted somatic variants (variant allele frequencies ranging from 100% to 5%), we observed significantly different calling efficiencies. In particular, despite relatively high specificity, sensitivity was poor in both pipelines resulting in a high rate of false negatives. Our findings raise the possibility that landscapes of AML genomes might be more complex than previously reported and characterized by the presence of hundreds of genes mutated at low variant allele frequency, suggesting that the application of genome sequencing to the clinic requires a careful and critical evaluation. We think that improvements in technology and workflow standardization, through the generation of clear experimental and bioinformatics guidelines, are fundamental to translate the use of next-generation sequencing from research to the clinic and to transform genomic information into better diagnosis and outcomes for the patient.

scholarly journals Prognostic Value of MicroRNA-20b in Acute Myeloid Leukemia

2021 ◽  
Vol 10 ◽  
Author(s):  
Zhiheng Cheng ◽  
Yifeng Dai ◽  
Wenhui Huang ◽  
Qingfu Zhong ◽  
Pei Zhu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Prognostic Impact ◽  
Hematopoietic Stem ◽  
Fine Grained ◽  
Low Expression ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous disease that requires fine-grained risk stratification for the best prognosis of patients. As a class of small non-coding RNAs with important biological functions, microRNAs play a crucial role in the pathogenesis of AML. To assess the prognostic impact of miR-20b on AML in the presence of other clinical and molecular factors, we screened 90 AML patients receiving chemotherapy only and 74 also undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. In the chemotherapy-only group, high miR-20b expression subgroup had shorter event-free survival (EFS) and overall survival (OS, both P < 0.001); whereas, there were no significant differences in EFS and OS between high and low expression subgroups in the allo-HSCT group. Then we divided all patients into high and low expression groups based on median miR-20b expression level. In the high expression group, patients treated with allo-HSCT had longer EFS and OS than those with chemotherapy alone (both P < 0.01); however, there were no significant differences in EFS and OS between different treatment subgroups in the low expression group. Further analysis showed that miR-20b was negatively correlated with genes in “ribosome,” “myeloid leukocyte mediated immunity,” and “DNA replication” signaling pathways. ORAI2, the gene with the strongest correlation with miR-20b, also had significant prognostic value in patients undergoing chemotherapy but not in the allo-HSCT group. In conclusion, our findings suggest that high miR-20b expression is a poor prognostic indicator for AML, but allo-HSCT may override its prognostic impact.

Sign in / Sign up

Export Citation Format

Share Document