Evidence map›Paper›PMID 40217071›Full record

ArticleLeukemia2025

Interferon-γ-mediated selective inhibition of hematopoiesis and the clonal advantage of HLA-lacking hematopoietic stem progenitor cells in aplastic anemia.

Rio Takahashi, Honoka Takahashi, Luna Seoka, Hiroka Iwasaki, Hiroyuki Takamatsu, Tatsuya Imi, Yoshitaka Zaimoku, Kohei Hosokawa, Takamasa Katagiri

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Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
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  5. 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

9 authors.

Rio TakahashiDepartment of Clinical Laboratory Science, Graduate School of Medical Science, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Honoka TakahashiDepartment of Clinical Laboratory Science, Graduate School of Medical Science, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Luna SeokaDepartment of Clinical Laboratory Science, Graduate School of Medical Science, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Hiroka IwasakiDepartment of Clinical Laboratory Science, Graduate School of Medical Science, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Hiroyuki TakamatsuDepartment of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
Tatsuya ImiDepartment of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.ORCID 0000-0002-7674-7368
Yoshitaka ZaimokuDepartment of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.ORCID 0000-0002-4108-5245
Kohei HosokawaDepartment of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.ORCID 0000-0002-3423-1523
Takamasa KatagiriDepartment of Clinical Laboratory Science, Graduate School of Medical Science, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan. takama@staff.kanazawa-u.ac.jp.ORCID 0000-0002-9568-8682

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) JP23K07829Takeda Science Foundation NA
6 · The paper itself

Abstract

Acquired aplastic anemia (AA) is an immune-mediated bone marrow failure caused by autoreactive cytotoxic T lymphocytes targeting hematopoietic stem progenitor cells (HSPCs). Approximately 30% of AA patients exhibit leukocytes lacking HLA class I alleles (HLA[-]). In addition to this direct immune assault, the pathogenesis of AA is thought to involve indirect suppression mediated by the proinflammatory cytokine interferon-gamma (IFN-γ). Using HSPCs derived from induced pluripotent stem cells (iPSCs) with different HLA genotypes, HLA(-) HSPCs were found to be resistant to the suppressive effects of IFN-γ, whereas IFN-γ effectively suppressed the growth and development of HSPCs expressing HLA class I molecules. Further analysis showed that, in contrast to HLA(-) HSPCs, WT HSPCs showed enhanced CD119 expression in response to IFN-γ, activating downstream signaling pathways that promote apoptosis, suggesting that transcription factors involved in the apoptotic pathway following IFN-γ stimulation are differentially expressed between WT and HLA(-) HSPCs. Notably, IFN-γ stimulation reduced the expression of pSTAT3, a key regulator of apoptosis, in WT HSPCs, whereas its expression was elevated in HLA(-) HSPCs. In conclusion, this study showed that the selective hematopoietic inhibition of HSPCs by IFN-γ likely facilitates clonal hematopoiesis and contributes to the persistence of HLA(-) HSPCs in patients with AA.

Indexed as

Anemia, AplasticHematopoiesisHematopoietic Stem CellsHLA AntigensInterferon-gammaApoptosisHumansInduced Pluripotent Stem CellsSTAT3 Transcription FactorHLA AntigensInterferon-gammaSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID40217071

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.