Dynamic mRNA expression of donor-derived activating KIR genes and their significant effects on clinical outcome after haematopoietic stem cell transplantation

Li, Ying; Hu, Xinting; Zhang, Huanhuan; Bao, Xiaojing; Wu, Depei; He, Jun

doi:10.1111/cei.13631

Cited by 2 publications

(1 citation statement)

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“…KIR2DS4, a killer-cell immunoglobulin-like receptor (KIR), involves in natural immunity. Increased activating KIRs (aKIRs) lead to hyperactivation of AML cells by NK cells and ultimately lead to disease progression [29].…”

Section: Discussionmentioning

confidence: 99%

The potential novel immune-related prognostic factors for acute myeloid leukemia

Zheng

et al. 2022

Preprint

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Background The pathological progression in acute myeloid leukemia (AML) was significantly affected by the immune microenvironment of bone marrow, where the immune-related genes (IRGs) and immune cells are involved in the prognosis of the disease. Studying immune-related components provide new ideas for treatment. Methods The transcriptome data and clinical information of 151 TCGA-LAML and 337 GTEx-whole-blood cohorts were downloaded from the UCSC Xena database. The IRGs were obtained from ImmPort database. Differentially expressed IRGs (DEIGs) were obtained from differentially expressed genes (DEGs). A prognostic model was constructed by COX regression analysis and verified by Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves in the training and validation cohorts (GEO37642 cohort). The relationship between gene expression level and prognosis was analyzed by K-M method. The independent prognostic factors were screened by univariate and multivariate Cox regression analysis. Relative immune cell composition of AML and healthy samples was calculated using the CIBERSORT algorithm. Results Enrichment analysis revealed that the immune cells and immune-related biology functions participated in AML progression. A prognostic model containing eight genes was constructed. In the training and validation cohorts, the survival rate of the low-risk group was significantly higher than that of the high-risk group. The area under the curve (AUC) values of ROC curves were ≥ 0.7. Among the model, high expression of CANX (P = 0.012), CLEC11A (P = 0.016), and TRH (P = 1.256E-04) was associated with a higher survival rate, while high expression of IL3RA (P = 0.038), KIR2DS4 (P = 0.016), APOBEC3G (P = 1.426E-04), and CKLF (P = 0.015) was associated with lower survival rate. The CANX expression level may affect the sensitivity of some drugs. Age, karyotype, and risk score are independent prognostic factors for AML. The differential level of 17 immune cells was observed between the AML and healthy samples. The levels of Macrophages M1, T cells follicular helper, and T cells CD8 were positively correlated with survival rate. Discussions The prognostic model may be helpful in predicting patient outcomes and 7 IRGs and 3 immune cells may be potential biomarkers and immunotherapy targets for AML in the future.

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Section: Discussionmentioning

confidence: 99%

The potential novel immune-related prognostic factors for acute myeloid leukemia

Zheng

et al. 2022

Preprint

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Dynamic mRNA expression of donor-derived activating KIR genes and their significant effects on clinical outcome after haematopoietic stem cell transplantation

Zhang

et al. 2021

Clinical and Experimental Immunology

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Numerous reports suggest that activating killer immunoglobulin-like receptors (aKIRs) of natural killer (NK) cells, in addition to inhibitory KIRs (iKIRs), play a prognostic role after allogeneic haematopoietic stem cell transplantation (allo-HSCT). We aimed to investigate the association between the dynamic expression of KIRs on NK cells and the outcomes, particularly regarding graftversus-host disease (GvHD). This study retrospectively enrolled 260 pairs of donors and recipients who had undergone allo-HSCT without in-vitro T cell depletion. The mRNA transcription level of KIRs was determined by quantitative real-time polymerase chain reaction (RT-qPCR). The levels of aKIR transcripts were decreased more than those of iKIRs during the occurrence of GvHD. The transcription levels of KIR2DS2 and KIR2DS4 in the patients developing GvHD, compared with those who were at a tolerance state, showed the most significant decrease in the month at their peak transcription levels (p = 0.03, p = 0.002). Significantly decreased expression of KIR2DS1 (p = 0.02), KIR2DS3 (p = 0.04) and KIR2DS5 (p = 0.04) in the GvHD group was observed when the transcription level reached a maximum. High expression of KIR3DS1 was associated with superior overall survival (OS) (p < 0.001). The expression of KIR2DS4 in the KIR genotype Bx group decreased more during GvHD, particularly at 3M (p = 0.02). These findings suggest that KIR genes are potential post-HSCT biomarkers and dynamic changes in the KIR transcription levels can be detected to better predict the occurrence and evaluate the treatment of GvHD after transplantation. K E Y W O R D SGvHD, KIR gene, mRNA expression, NK cell, quantitative real-time polymerase chain reaction

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Dynamic mRNA expression of donor-derived activating KIR genes and their significant effects on clinical outcome after haematopoietic stem cell transplantation

Cited by 2 publications

References 43 publications

The potential novel immune-related prognostic factors for acute myeloid leukemia

The potential novel immune-related prognostic factors for acute myeloid leukemia

Dynamic mRNA expression of donor-derived activating KIR genes and their significant effects on clinical outcome after haematopoietic stem cell transplantation

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