Evidence map›Paper›PMID 38914715›Full record

ArticleLeukemia2024

Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia.

Ryo Yanagiya, Yuji Miyatake, Natsumi Watanabe, Takanobu Shimizu, Akane Kanamori, Masaya Ueno, Sachiko Okabe, Joaquim Carreras, Shunya Nakayama, Ami Hasegawa and 15 more

Abstract read
In one paragraph

Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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

25 authors.

Ryo YanagiyaDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.ORCID 0000-0002-2092-8194
Yuji MiyatakeDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Natsumi WatanabeDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Takanobu ShimizuDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Akane KanamoriDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Masaya UenoDivision of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Japan.ORCID 0000-0001-9177-8640
Sachiko OkabeDivision of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Joaquim CarrerasDepartment of Pathology, Tokai University School of Medicine, Isehara, Japan.ORCID 0000-0002-6129-8299
Shunya NakayamaDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Ami HasegawaDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Kazuaki KamedaDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan.
Takeshi KamakuraDepartment of Regulation of Infectious Cancers, Division of Cellular and Molecular Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
So NakagawaDepartment of Molecular Life Science, Tokai University School of Medicine, Isehara, Japan.
Takuji YamauchiDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Takahiro MaedaDivision of Precision Medicine, Kyushu University Hospital, Fukuoka, Japan.ORCID 0000-0003-4530-6460
Keisuke IshiiPerseus Proteomics, Inc, Tokyo, Japan.
Tadashi MatsuuraPerseus Proteomics, Inc, Tokyo, Japan.
Hiroshi HandaDepartment of Hematology, Gunma University Graduate School of Medicine, Maebashi, Japan.ORCID 0000-0003-3753-9862
Atsushi HiraoDivision of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Japan.ORCID 0000-0001-7818-8240
Kenichi IshizawaDepartment of Neurology, Hematology, Diabetology, Endocrinology, and Metabolism (3rd Department of Internal Medicine), Faculty of Medicine, Yamagata University, Yamagata, Japan.
Makoto OnizukaDepartment of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan.
Tetsuo MashimaDivision of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Naoya NakamuraDepartment of Pathology, Tokai University School of Medicine, Isehara, Japan.
Kiyoshi AndoDepartment of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan.
Ai KotaniDepartment of Innovative Medical Science, Tokai University School of Medicine, Isehara, Japan. aikotani@k-lab.jp.ORCID 0000-0002-0976-8687

Funding

Japan Agency for Medical Research and Development (AMED) 22ama221213h0002Japan Agency for Medical Research and Development (AMED) 23ama221216h0002Japan Agency for Medical Research and Development (AMED) 23fk0210133s0401MEXT | Japan Science and Technology Agency (JST) JPMJCR19H5MEXT | Japan Society for the Promotion of Science (JSPS) JP22H04922MEXT | Japan Society for the Promotion of Science (JSPS) JP23H02940MEXT | Japan Society for the Promotion of Science (JSPS) JP23K14629MEXT | Japan Society for the Promotion of Science (JSPS) JP24K19229
6 · The paper itself

Abstract

Aggressive natural killer cell leukemia (ANKL) is a rare hematological malignancy with a fulminant clinical course. Our previous study revealed that ANKL cells proliferate predominantly in the liver sinusoids and strongly depend on transferrin supplementation. In addition, we demonstrated that liver-resident ANKL cells are sensitive to PPMX-T003, an anti-human transferrin receptor 1 inhibitory antibody, whereas spleen-resident ANKL cells are resistant to transferrin receptor 1 inhibition. However, the microenvironmental factors that regulate the iron dependency of ANKL cells remain unclear. In this study, we first revealed that the anti-neoplastic effect of PPMX-T003 was characterized by DNA double-strand breaks in a DNA replication-dependent manner, similar to conventional cytotoxic agents. We also found that the influx of extracellular amino acids via LAT1 stimulated sensitivity to PPMX-T003. Taken together, we discovered that the amount of extracellular amino acid influx through LAT1 was the key environmental factor determining the iron dependency of ANKL cells via adjustment of their mTOR/Myc activity, which provides a good explanation for the different sensitivity to PPMX-T003 between liver- and spleen-resident ANKL cells, as the liver sinusoid contains abundant amino acids absorbed from the gut.

Indexed as

Amino AcidsIronKiller Cells, NaturalLarge Neutral Amino Acid-Transporter 1AnimalsHumansLiverMiceReceptors, TransferrinAmino AcidsIronLarge Neutral Amino Acid-Transporter 1Receptors, TransferrinSLC7A5 protein, human

Identifiers

PMID38914715
PMCPMC11286515

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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.