The role of NFAT in the pathogenesis and targeted therapy of hematological malignancies

Gao, Rili; Zhang, Yikai; Zeng, Chengwu; Li, Yangqiu

doi:10.1016/j.ejphar.2022.174889

Cited by 6 publications

(4 citation statements)

References 73 publications

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“… 31 NFATC1 has been implicated in the pathogenesis and targeted therapy of hematological malignancies. 32 , 33 rs657693 is a cis- pQTL for NFATC1 in the UKB PPP GWAS and one of only two genetic associations for this protein. rs657693 is identified here as an rQTL for the ratio of NFATC1 with 16 other proteins (AXIN1, BACH1, BANK1, BCR, CASP2, CD69, EIF4G1, FADD, FOXO1, IKBKG, INPPL1, IRAK1, LBR, PTPN6, SPRY2, TJAP1; Table S4 ), none of which had a significant association with this variant alone.…”

Section: Resultsmentioning

confidence: 99%

Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions

Suhre

2024

Cell Genomics

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Section: Resultsmentioning

confidence: 99%

Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions

Suhre

2024

Cell Genomics

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“…NFATC1 has been implicated in the pathogenesis and targeted therapy of hematological malignancies 29,30 . rs657693 is a cis-pQTL for NFATC1 in the UKB PPP GWAS and one of only two genetic association for this protein.…”

Section: What Can Be Learned From Rqtls?mentioning

confidence: 99%

Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions

Suhre

2023

Preprint

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Protein quantitative trait loci (pQTLs) are an invaluable source of information for drug target development as they provide genetic evidence to support protein function, suggest relationships between cis- and trans-associated proteins, and link proteins to disease where they collocate with genetic risk loci for clinical endpoints. Using the recently released Olink proteomics data for 1,463 proteins measured in over 54,000 samples of the UK Biobank we identified and replicated 4,248 associations with 2,821 ratios between protein levels (rQTLs) where the strengths of association at known pQTL loci increased by up to several hundred orders of magnitude. We attribute this increase in statistical power (p-gain) to accounting for genetic and non-genetic variance shared by the two proteins in the ratio pair. Protein pairs with a significant p-gain were 7.6-fold enriched in known protein-protein interactions, suggesting that their ratios reflect biological links between the implicated proteins. We then conducted a GWAS on the 2,821 ratios and identified 2,527 novel rQTLs, increasing the number of discovered genetic signals compared to the original protein-only GWAS by 24.7%. At examples we demonstrate that this approach can identify novel loci of clinical relevance, support causal gene identification, and reveal complex networks of interacting proteins. Taken together, our study adds significant value to the genetic insights that can be derived from the UKB proteomics data and motivates the wider use of ratios in large scale GWAS.

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“…TCRs include four peptide chains, α, β, γ, and δ. α and β peptide chains form αβ TCRs, while γ and δ peptide chains form γδ TCRs [ 17 , 18 ]. αβ TCRs activate the TCR signaling pathway by binding to the major histocompatibility complex (MHC) on tumor cells or antigen presenting cells (APCs), which then activates a series of intracellular proteins including CD3ζ, 70-kD zeta-associated protein (ZAP70), and nuclear factor of activated T cells 2 (NFAT2), thereby mediating T cell immune function [ 18 , 19 ]. TCR-T cells are constructed by transferring a TCR gene sequence that specifically recognizes tumor antigens into T cells through genetic engineering so that the T cells have the ability to specifically kill tumor cells [ 1 , 20 ].…”

Section: Tcr-t Cell Constructionmentioning

confidence: 99%

TCR engineered T cells for solid tumor immunotherapy

et al. 2022

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T cell immunotherapy remains an attractive approach for cancer immunotherapy. T cell immunotherapy mainly employs chimeric antigen receptor (CAR)- and T cell receptor (TCR)-engineered T cells. CAR-T cell therapy has been an essential breakthrough in treating hematological malignancies. TCR-T cells can recognize antigens expressed both on cell surfaces and in intracellular compartments. Although TCR-T cells have not been approved for clinical application, a number of clinical trials have been performed, particularly for solid tumors. In this article, we summarized current TCR-T cell advances and their potential advantages for solid tumor immunotherapy.

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The role of NFAT in the pathogenesis and targeted therapy of hematological malignancies

Cited by 6 publications

References 73 publications

Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions

Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions

Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions

TCR engineered T cells for solid tumor immunotherapy

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