Evidence map›Paper›PMID 42056531›Full record

ArticleLeukemia2026

Multi-omics analysis of pediatric minimally differentiated acute myeloid leukemia reveals RUNX1-driven stemness and chemoresistance.

Tatsuya Kamitori, Satoshi Saida, Kazuki Mitani, Shinichi Tsujimoto, Hiroaki Goto, Hirofumi Shibata, Ryo Akazawa, Kiyotaka Isobe, Hiroo Ueno, Nobuyuki Kakiuchi and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

28 authors.

Tatsuya KamitoriDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0009-0003-0472-4663
Satoshi Saida *Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. satoshi@kuhp.kyoto-u.ac.jp.ORCID http://orcid.org/0000-0002-8930-3539
Kazuki MitaniDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Shinichi TsujimotoDepartment of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.ORCID http://orcid.org/0000-0001-5738-4138
Hiroaki GotoDivision of Hematology/Oncology, Kanagawa Children's Medical Center, Yokohama, Japan.
Hirofumi ShibataDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ryo AkazawaDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kiyotaka IsobeDepartment of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
Hiroo UenoDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nobuyuki KakiuchiDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0003-4893-5414
Akiko M SaitoClinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan.ORCID http://orcid.org/0000-0003-3723-8445
Mitsuteru HiwatariDepartment of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan.
Ko KudoDepartment of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.ORCID http://orcid.org/0000-0001-8214-1787
Shinsuke HirabayashiDepartment of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.
Kohei FukuokaDepartment of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
Katsuyoshi KohDepartment of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.ORCID http://orcid.org/0000-0002-0476-4978
Takashi TagaDepartment of Pediatrics, Shiga University of Medical Science, Otsu, Japan.ORCID http://orcid.org/0000-0003-0525-4766
Hirohito KubotaDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0002-6935-5120
Itaru KatoDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0002-2932-4960
Katsutsugu UmedaDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0002-6844-2011
Souichi AdachiHuman Health Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tomoko KawaiDepartment of Maternal Fetal Biology, National Center for Child Health and Development, Tokyo, Japan.
Daisuke TomizawaDivision of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.ORCID http://orcid.org/0000-0003-1520-7007
Junji IkedaDepartment of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Norio ShibaDepartment of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Yasuhide HayashiGunma Children's Medical Center, Shibukawa, Japan.
Seishi OgawaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Junko Takita *Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. jtakita@kuhp.kyoto-u.ac.jp.ORCID http://orcid.org/0000-0002-2452-6520

Funding

Japan Agency for Medical Research and Development (AMED) JP19cm0106509, JP22ana221505, JP23ama221505, JP24ama221531, JP25ama221531, and JP19ck0106468MEXT | Japan Society for the Promotion of Science (JSPS) JP18K19467, JP20H00528, JP21K19405, JP23K18264, JP24H00628, and JP25K22609MEXT | Japan Society for the Promotion of Science (JSPS) JP20K16923 and JP24K10953
6 · The paper itself

Abstract

Minimally differentiated acute myeloid leukemia (AML-M0) is a rare and therapeutically challenging subgroup of AML characterized by immature hematopoietic stem cell-like features. To uncover the molecular basis, we conducted a comprehensive multi-omics analysis of 23 pediatric AML-M0 cases and compared them with 1483 leukemia samples. AML-M0 formed a characteristic group that exhibited global DNA hypermethylation and transcriptional suppression, particularly downregulation of genes related to oxidative phosphorylation and ribosome assembly compared to non-M0 AML. Genomic profiling revealed frequent loss-of-function alterations in RUNX1 (26%) and ETV6 (22%), along with activating mutations in signaling pathways (83%), such as RAS, FLT3, and JAK. Notably, RUNX1 alterations were significantly associated with a poor prognosis. Functional analyses using a CRISPR/Cas9-mediated RUNX1 knockout in a pediatric AML-M0 cell line showed stem cell-like transcriptional features and reduced expression of genes related to oxidative phosphorylation and ribosomal pathways. RUNX1 disruption was also associated with reduced in vitro sensitivity to multiple drugs, including cytarabine and anthracyclines. Our study provides the most comprehensive molecular characterization of pediatric AML-M0 to date and identifies RUNX1 alterations as important biological and clinical determinants. These insights highlight the potential strategies for precision therapy, including hypomethylating agents, signaling inhibitors, and metabolic targeting, to improve outcomes.

Indexed as

Core Binding Factor Alpha 2 SubunitDrug Resistance, NeoplasmLeukemia, Myeloid, AcuteNeoplastic Stem CellsAdolescentCell DifferentiationChildChild, PreschoolDNA MethylationFemaleGene Expression ProfilingGene Expression Regulation, LeukemicHumansMaleMultiomicsMutationCore Binding Factor Alpha 2 SubunitRUNX1 protein, human

Identifiers

PMID42056531
PMCPMC13322964

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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.