Evidence map›Paper›PMID 40875517›Full record

ArticleCancer science2025

CTCF Is Essential for the Development and Maintenance of CALM-AF10-Induced Leukemia.

Yoko Kuroki, Kazutsune Yamagata, Yukiko Aikawa, Yutaka Shima, Hisafumi Shioneri, Issay Kitabayashi

Abstract read
In one paragraph

Article in Cancer science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Yoko KurokiCenter for Translational Research, Fujita Health University, Aichi, Japan.
Kazutsune YamagataDivision of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.
Yukiko AikawaDivision of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.
Yutaka ShimaCenter for Translational Research, Fujita Health University, Aichi, Japan.
Hisafumi ShioneriCenter for Translational Research, Fujita Health University, Aichi, Japan.
Issay KitabayashiCenter for Translational Research, Fujita Health University, Aichi, Japan.ORCID https://orcid.org/0000-0002-8409-0407

Funding

Japan Agency for Medical Research and Development JP24ama221131h
6 · The paper itself

Abstract

CALM (Clathrin Assembly Lymphoid Myeloid Leukemia)-AF10, a fusion gene commonly associated with acute myeloid leukemia (AML), arises from the t(10;11) translocation and is linked to poor prognosis. In this study, we demonstrate that the CCCTC-binding factor (CTCF) plays a critical role in both the initiation and maintenance of CALM-AF10-induced AML (CALM-AF10 AML). In vivo, CTCF deficiency significantly extended the survival of CALM-AF10 AML mice. In vitro, CTCF knockout (KO) reduced the colony-forming capacity of CALM-AF10 AML cells and induced their differentiation into macrophage-like cells. RNA sequencing (RNA-seq) of CTCF KO cells revealed that Transglutaminase 2 (TGM2) was the most significantly downregulated gene. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis indicated increased repressive histone mark, H3K27 trimethylation (H3K27me3), accompanied by reduced active histone marks, including H3K4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac), at the transcription start site (TSS) of Tgm2 following CTCF KO. Knockdown of Tgm2 using short hairpin RNA (shRNA) in CALM-AF10 AML cells and in the human leukemic cell line U937 harboring the CALM-AF10 fusion gene resulted in reduced colony formation and proliferation. This also promoted differentiation into macrophage-like cells, recapitulating the effects observed with CTCF KO. Similarly, comparable outcomes were observed with GK921, a TGM2 inhibitor, highlighting the impact of TGM2 blockade. These findings suggest that CTCF regulates TGM2 expression by modulating post translational modifications of histones at its TSS, thereby preserving the undifferentiated state of CALM-AF10 AML cells. The demonstrated efficacy of TGM2 inhibitors further underscores the importance of TGM2 in this subtype of leukemia.

Indexed as

CCCTC-Binding FactorLeukemia, Myeloid, AcuteOncogene Proteins, FusionAnimalsCell DifferentiationCell Line, TumorGene Expression Regulation, LeukemicGTP-Binding ProteinsHistonesHumansMiceMice, KnockoutProtein Glutamine gamma Glutamyltransferase 2TransglutaminasesCCCTC-Binding FactorCTCF protein, humanCtcf protein, mouseGTP-Binding ProteinsHistonesOncogene Proteins, FusionProtein Glutamine gamma Glutamyltransferase 2TGM2 protein, humanTransglutaminasesacute myeloid leukemiaCALM‐AF10CCCTC‐binding factorepigenetic regulationTransglutaminase 2

Identifiers

PMID40875517
PMCPMC12580881

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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.