Evidence map›Paper›PMID 42080957›Full record

ArticleNaunyn-Schmiedeberg's archives of pharmacology2026

Combined inhibition of DOT1L and BCL-2 induces synergistic anti-leukemic effects in MLL-rearranged acute myeloid leukemia via suppression of the PI3K/AKT pathway.

Yabei Zuo, Li Geng, Yujie Guo, Daitianchang Zhao, Nannan Qi, Yan Wang, Jingyu Zhang, Zhiyun Niu

Abstract read
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In one paragraph

Article in Naunyn-Schmiedeberg's archives of pharmacology, 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

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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

8 authors.

Yabei ZuoDepartment of Hematology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei, 050000, China.
Li GengDepartment of Hematology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei, 050000, China.
Yujie GuoDepartment of Hematology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei, 050000, China.
Daitianchang ZhaoGraduate School, Hebei Medical University, Shijiazhuang, Hebei, China.
Nannan QiGraduate School, Hebei Medical University, Shijiazhuang, Hebei, China.
Yan WangDepartment of Hematology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei, 050000, China.
Jingyu ZhangDepartment of Hematology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei, 050000, China.
Zhiyun NiuDepartment of Hematology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, Hebei, 050000, China. zhiyunniu@hebmu.edu.cn.

Funding

Central Government Guidance Funds for Local Scientific and Technological Development, China 236Z7736GHebei Provincial Health Commission Government-Funded Clinical Medicine Talent Program ZF2024048
6 · The paper itself

Abstract

MLL-rearranged acute myeloid leukemia (AML) is a high-risk hematological malignancy driven by aberrant epigenetic regulation. MLL fusion proteins recruit the DOT1L methyltransferase, causing dysregulated histone H3K79 methylation and sustained leukemogenic gene expression (HOXA10, MLLT10), while BCL-2 overexpression contributes to apoptosis resistance. This study evaluated the synergistic efficacy of combining the DOT1L inhibitor EPZ004777 with the BCL-2 inhibitor ABT-737. THP-1 cells were treated with EPZ004777 and ABT-737 alone or in combination. Cell proliferation, apoptosis, H3K79 methylation, target gene expression, and PI3K/AKT signaling were assessed. An in vivo xenograft mouse model (C-NKG mice) validated therapeutic effects. Combined treatment exhibited potent synergistic cytotoxicity. Dual inhibition reduced H3K79 di- and tri-methylation, downregulated HOXA10 and MLLT10, and blocked PI3K/AKT phosphorylation. In vivo, combination therapy prolonged survival, restored bone marrow function, and alleviated organ infiltration. These findings demonstrate that dual targeting of DOT1L and BCL-2 exerts synergistic anti-leukemic activity via PI3K/AKT suppression in MLL-rearranged AML, providing a pharmacological rationale for this innovative combination strategy.

Indexed as

Antineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiphenyl CompoundsHistone-Lysine N-MethyltransferaseLeukemia, Myeloid, AcuteMyeloid-Lymphoid Leukemia ProteinNitrophenolsProto-Oncogene Proteins c-bcl-2SulfonamidesAdenosineAnimalsApoptosisCell ProliferationDrug SynergismGene RearrangementHumansABT-737AdenosineAntineoplastic AgentsBiphenyl CompoundsDOT1L protein, humanEPZ004777Histone-Lysine N-MethyltransferaseKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinNitrophenolsPhenylurea CompoundsPhosphatidylinositol 3-KinasesPiperazinesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-bcl-2SulfonamidesBCL-2 inhibitorCombination therapyDOT1L inhibitorMLL-rearranged AMLPI3K/AKTSynergistic effect

Identifiers

PMID42080957

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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.