A comprehensive assessment of the prognostic role of cell adhesion molecules in acute myeloid leukemia

Cheng, Jing; Han, Juan; Chen, Lin

doi:10.21037/tcr-20-3315

Cited by 5 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, ITGA4 expression was also detected on several healthy hematopoietic cells, which might impact the suitability of ITGA4 as a single target antigen. Studies on the prognostic role of ITGA4 expression in AML are very limited [31], thus we expect future studies to illuminate its role further.…”

Section: Discussionmentioning

confidence: 99%

Integrated multiomic approach for identification of novel immunotherapeutic targets in AML

Köhnke

Liu²,

Haubner

et al. 2022

Biomark Res

View full text Add to dashboard Cite

Background Immunotherapy of acute myeloid leukemia has experienced considerable advances, however novel target antigens continue to be sought after. To this end, unbiased approaches for surface protein detection are limited and integration with other data types, such as gene expression and somatic mutational burden, are poorly utilized. The Cell Surface Capture technology provides an unbiased, discovery-driven approach to map the surface proteins on cells of interest. Yet, direct utilization of primary patient samples has been limited by the considerable number of viable cells needed. Methods Here, we optimized the Cell Surface Capture protocol to enable direct interrogation of primary patient samples and applied our optimized protocol to a set of samples from patients with acute myeloid leukemia (AML) to generate the AML surfaceome. We then further curated this AML surfaceome to exclude antigens expressed on healthy tissues and integrated mutational burden data from hematologic cancers to further enrich for targets which are likely to be essential to leukemia biology. Finally, we validated our findings in a separate cohort of AML patient samples. Results Our protocol modifications allowed us to double the yield in identified proteins and increased the specificity from 54 to 80.4% compared to previous approaches. Using primary AML patient samples, we were able to identify a total of 621 surface proteins comprising the AML surfaceome. We integrated this data with gene expression and mutational burden data to curate a set of robust putative target antigens. Seventy-six proteins were selected as potential candidates for further investigation of which we validated the most promising novel candidate markers, and identified CD148, ITGA4 and Integrin beta-7 as promising targets in AML. Integrin beta-7 showed the most promising combination of expression in patient AML samples, and low or absent expression on healthy hematopoietic tissue. Conclusion Taken together, we demonstrate the feasibility of a highly optimized surfaceome detection method to interrogate the entire AML surfaceome directly from primary patient samples and integrate this data with gene expression and mutational burden data to achieve a robust, multiomic target identification platform. This approach has the potential to accelerate the unbiased target identification for immunotherapy of AML.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrated multiomic approach for identification of novel immunotherapeutic targets in AML

Köhnke

Liu²,

Haubner

et al. 2022

Biomark Res

View full text Add to dashboard Cite

show abstract

“… 38 – 40 In a systematic analysis of cellular adhesion molecule expression signatures, additional data showed that ICAM2 was inversely associated with overall survival in AML patients, which further supported our results. 41 We demonstrated that patients with intermediate ELN-2017 risk were still significantly stratified by ICAM2 expression, which was an independent predictor of clinical outcome in multivariate regression analysis. There was a strong association between ICAM2 status and OS, even after accounting for age and the potential effects of bone marrow transplantation.…”

Section: Discussionmentioning

confidence: 71%

Serum proteomics screening intercellular adhesion molecule-2 improves intermediate-risk stratification in acute myeloid leukemia

Zhang

Liu

et al. 2022

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

Background: The clinical risk classification of acute myelocytic leukemia (AML) is largely based on cytogenetic and molecular genetic detection. However, the optimal treatment for intermediate-risk AML patients remains uncertain. Further refinement and improvement of prognostic stratification are therefore necessary. Objectives: The aim of this study was to identify serum protein biomarkers to refine risk stratification in AML patients. Design: This study is a retrospective study. Methods: Label-free proteomics was used to identify the differential abundance of serum proteins in AML patients. Transcriptomic data were combined to identify key altered markers that could indicate the risk rank of AML patients. The survival status was assessed by Kaplan–Meier and multivariate Cox regression analyses. Results: We delineated serum protein expression in a population of AML patients. Many biological processes were influenced by the identified differentially expressed proteins. Association analysis of transcriptome data showed that intercellular adhesion molecule-2 (ICAM2) had a higher survival prediction value in the intermediate-risk AML group. ICAM2 was detrimental for intermediate-risk AML, regardless of whether patients received bone marrow transplantation. ICAM2 well distinguishes the intermediate group of patients, whose probability of survival is comparable to that of patients with the ELN-2017 according to the reference classification. In addition, newly established stratified clinical features were associated with leukemia stem cell scores. Conclusion: The inclusion of ICAM2 expression into the AML risk classification according to ELN-2017 was a good way to transfer patients from three to two groups. Thus, providing more information for clinical decision-making to improve intermediate-risk stratification in AML patients.

show abstract

“…Tryndyak et al reported that cytosine DNA hypermethylation induced the downregulation of CLDN14 gene expression in differentiated HepaRG cells treated with NaAsO 2 ( 64 ). Another study revealed that the CLDN14 expression level was negatively correlated with acute myeloid leukemia (AML) survival rates ( 65 ). In breast cancer (BC), CLDN14 gene expression was upregulated in BC tissues compared with non-cancer tissues, and a high gene expression of CLDN14 was associated with a poor overall survival ( 66 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules

Bolatkan

Asada²,

Kaneko³

et al. 2021

Int J Oncol

View full text Add to dashboard Cite

RNA modifications have attracted increasing interest in recent years because they have been frequently implicated in various human diseases, including cancer, highlighting the importance of dynamic post-transcriptional modifications. Methyltransferase-like 6 (METTL6) is a member of the RNA methyltransferase family that has been identified in many cancers; however, little is known about its specific role or mechanism of action. In the present study, we aimed to study the expression levels and functional role of METTL6 in hepatocellular carcinoma (HCC), and further investigate the relevant pathways. To this end, we systematically conducted bioinformatics analysis of METTL6 in HCC using gene expression data and clinical information from a publicly available dataset. The mRNA expression levels of METTL6 were significantly upregulated in HCC tumor tissues compared to that in adjacent non-tumor tissues and strongly associated with poorer survival outcomes in patients with HCC. CRISPR/Cas9-mediated knockout of METTL6 in HCC cell lines remarkably inhibited colony formation, cell proliferation, cell migration, cell invasion and cell attachment ability. RNA sequencing analysis demonstrated that knockout of METTL6 significantly suppressed the expression of cell adhesion-related genes. However, chromatin immunoprecipitation sequencing results revealed no significant differences in enhancer activities between cells, which suggests that METTL6 may regulate genes of interest post-transcriptionally. In addition, it was demonstrated for the first time that METTL6 was localized in the cytosol as detected by immunofluorescence analysis, which indicates the plausible location of RNA modification mediated by METTL6. Our findings provide further insight into the function of RNA modifications in cancer and suggest a possible role of METTL6 as a therapeutic target in HCC.

show abstract

A comprehensive assessment of the prognostic role of cell adhesion molecules in acute myeloid leukemia

Cited by 5 publications

References 22 publications

Integrated multiomic approach for identification of novel immunotherapeutic targets in AML

Integrated multiomic approach for identification of novel immunotherapeutic targets in AML

Serum proteomics screening intercellular adhesion molecule-2 improves intermediate-risk stratification in acute myeloid leukemia

Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules

Contact Info

Product

Resources

About