Evidence map›Paper›PMID 40320412›Full record

ArticleSignal transduction and targeted therapy2025

Overexpressing natural killer group 2 member A drives natural killer cell exhaustion in relapsed acute myeloid leukemia.

Juan Xie, Xue-Fei Liu, Tong Zhou, Long Liu, Rui-Qin Hou, Xing-Xing Yu, Ze-Ying Fan, Qian-Nan Shang, Ying-Jun Chang, Xiao-Su Zhao and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. The CD94/NKG2A-HLA-E Axis as a Target in Cancer Immunotherapy: A Critical Perspective.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Novel Therapeutics for Hepatocellular Carcinoma.Clinics in liver disease · 2025
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Juan Xie *Peking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Xue-Fei Liu *Peking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Tong Zhou *Peking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Long LiuPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Rui-Qin HouPeking University People's Hospital department of blood transfusion, No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Xing-Xing YuPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Ze-Ying FanPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Qian-Nan ShangPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Ying-Jun ChangPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Xiao-Su ZhaoPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Yu WangPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Lan-Ping XuPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.ORCID 0000-0002-0267-1081
Xiao-Hui ZhangPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.
Xiao-Jun HuangPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China. huangxiaojun@bjmu.edu.cn.
Xiang-Yu ZhaoPeking University People's Hospital, Institute of Hematology, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, National Clinical Research Centre for Hematologic Disease; No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China. zhao_xy@bjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute myeloid leukemia (AML) relapse is associated with poor prognosis. While natural killer (NK) cell therapy can induce leukemia remission, infused NK cells are prone to exhaustion. Elucidating the molecular mechanisms driving NK cell exhaustion in AML patients could provide critical insights for developing novel strategies to optimize NK cell-based immunotherapies. In this study, we systematically investigated NK cell exhaustion in relapsed AML patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) through phenotypic assessments, functional assays, and RNA sequencing analyses. Compared to NK cells from complete remission patients and healthy controls, NK cells from relapsed AML patients exhibited an exhausted phenotype, marked by reduced maturity, elevated expression of the inhibitory receptor NKG2A, impaired cytotoxicity, and suppression of the PI3K-AKT pathway. Notably, NKG2A expression levels on NK cells correlated with disease progression. Blockade or genetic knockout of NKG2A effectively reversed NK cell exhaustion both in vitro and in an AML mouse model. Furthermore, activation of the PI3K-AKT pathway significantly enhanced cytotoxicity in exhausted NK cells. We found that excessive activation of the NKG2A/HLA-E axis was associated with PI3K-AKT pathway inhibition, and blocking the NKG2A/HLA-E interaction or knocking out NKG2A restored AKT phosphorylation in exhausted NK cells. In summary, AML cells drive NK cell exhaustion through overactivation of the NKG2A/HLA-E axis and suppression of the PI3K-AKT pathway. Targeting the NKG2A/HLA-E axis represents a promising therapeutic approach to restore PI3K-AKT signaling and reverse NK cell exhaustion.

Indexed as

Killer Cells, NaturalLeukemia, Myeloid, AcuteNK Cell Lectin-Like Receptor Subfamily CAnimalsFemaleHematopoietic Stem Cell TransplantationHumansMaleMiceMiddle AgedPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionKLRC1 protein, humanNK Cell Lectin-Like Receptor Subfamily CPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-akt

Identifiers

PMID40320412
PMCPMC12050333

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.