Evidence map›Paper›PMID 30593567›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Different roles of E proteins in t(8;21) leukemia: E2-2 compromises the function of AETFC and negatively regulates leukemogenesis.

Na Liu, Junhong Song, Yangyang Xie, Xiao-Lin Wang, Bowen Rong, Na Man, Meng-Meng Zhang, Qunling Zhang, Fei-Fei Gao, Mei-Rong Du and 19 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 15% of its field
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

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. HSCs/MPPs as cells of origin with altered differentiation hierarchy impairing immunomicroenvironment inProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. LYL1 facilitates AETFC assembly and gene activation by recruiting CARM1 in t(8;21) AML.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Article
  11. Relationship between the structure and function of the transcriptional regulator E2A.Journal of biological research (Thessalonike, Greece) · 2021
    Review
  12. Review
  13. Review
  14. 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

29 authors at 8 institutions in 2 countries.

Na LiuChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Junhong SongKey Laboratory of Pediatric Hematology and Oncology, Ministry of Health, Department of Pediatric Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Yangyang XieKey Laboratory of Pediatric Hematology and Oncology, Ministry of Health, Department of Pediatric Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Xiao-Lin WangState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Bowen RongLiver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Epigenetics and Metabolism, Ministry of Science and Technology, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Na ManDepartment of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136.
Meng-Meng ZhangState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Qunling ZhangDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Fei-Fei GaoMaternity and Obstetrics Department, Shanghai Maternal and Child Health Center, Shanghai 200062, China.
Mei-Rong DuLaboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai Medical College, Fudan University, Shanghai 200011, China.
Ying ZhangLaboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai Medical College, Fudan University, Shanghai 200011, China.
Jian ShenDepartment of Gynecology and Obstetrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chun-Hui XuChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Cheng-Long HuChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ji-Chuan WuChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ping LiuChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Yuan-Liang ZhangState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Yin-Yin XieState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Ping LiuState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Jin-Yan HuangState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.ORCID 0000-0002-8053-0209
Qiu-Hua HuangState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Fei LanLiver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Epigenetics and Metabolism, Ministry of Science and Technology, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Shuhong ShenKey Laboratory of Pediatric Hematology and Oncology, Ministry of Health, Department of Pediatric Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Stephen D NimerDepartment of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136.
Zhu ChenState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Sai-Juan ChenState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Robert G RoederLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065 roeder@rockefeller.edu lwang@sibs.ac.cn xjsun@sibs.ac.cn.
Lan WangChinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; roeder@rockefeller.edu lwang@sibs.ac.cn xjsun@sibs.ac.cn.
Xiao-Jian SunState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; roeder@rockefeller.edu lwang@sibs.ac.cn xjsun@sibs.ac.cn.ORCID 0000-0001-8826-4614
Shanghai Jiao Tong University · CNShanghai Institute of Nutrition and Health · CNFudan University · CNUniversity of Miami · USFudan University Shanghai Cancer Center · CNObstetrics and Gynecology Hospital of Fudan University · CNRockefeller University · USShanghai Changning Maternity and Infant Health Hospital · CN

Funding

Tumor Biology Research ProgramP30CA240139 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI George S. Grills · 2019 to 2026
$24.1M
Targeting p300 and lysine acetylation in AMLR01CA166835 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Stephen D. Nimer · 2012 to 2026
$4.6M
Function and targeting of a stable transcription factor complex in leukemiaR01CA163086 · NCI · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2011 to 2022
$3.6M
Transcriptional regulatory mechanisms in B cell development and leukemogenesisR01CA178765 · NCI · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2013 to 2017
$2.8M
NCI NIH HHS P30 CA240139NCI NIH HHS R01 CA163086NCI NIH HHS R01 CA166835NCI NIH HHS R01 CA178765
6 · The paper itself

Abstract

The AML1-ETO fusion protein, generated by the t(8;21) chromosomal translocation, is causally involved in nearly 20% of acute myeloid leukemia (AML) cases. In leukemic cells, AML1-ETO resides in and functions through a stable protein complex, AML1-ETO-containing transcription factor complex (AETFC), that contains multiple transcription (co)factors. Among these AETFC components, HEB and E2A, two members of the ubiquitously expressed E proteins, directly interact with AML1-ETO, confer new DNA-binding capacity to AETFC, and are essential for leukemogenesis. However, the third E protein, E2-2, is specifically silenced in AML1-ETO-expressing leukemic cells, suggesting E2-2 as a negative factor of leukemogenesis. Indeed, ectopic expression of E2-2 selectively inhibits the growth of AML1-ETO-expressing leukemic cells, and this inhibition requires the bHLH DNA-binding domain. RNA-seq and ChIP-seq analyses reveal that, despite some overlap, the three E proteins differentially regulate many target genes. In particular, studies show that E2-2 both redistributes AETFC to, and activates, some genes associated with dendritic cell differentiation and represses MYC target genes. In AML patients, the expression of E2-2 is relatively lower in the t(8;21) subtype, and an E2-2 target gene,

Indexed as

Basic Helix-Loop-Helix ProteinsCell DifferentiationCell Line, TumorCore Binding Factor Alpha 2 SubunitHumansLeukemia, Myeloid, AcuteOncogene Proteins, FusionRecurrenceRUNX1 Translocation Partner 1 ProteinTranscription Factor 7-Like 2 ProteinAML1-ETO fusion protein, humanBasic Helix-Loop-Helix ProteinsCore Binding Factor Alpha 2 SubunitOncogene Proteins, FusionRUNX1 Translocation Partner 1 ProteinTCF12 protein, humanTCF3 protein, humanTCF7L2 protein, humanTranscription Factor 7-Like 2 Proteinacute myeloid leukemiaAETFCAML1-ETOdendritic cellE protein

Identifiers

PMID30593567
PMCPMC6338862
OpenAlexW2908176424

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.