Evidence map›Paper›PMID 28418922›Full record

ArticleOncotarget2017

Novel impact of the DNMT3A R882H mutation on GSH metabolism in a K562 cell model established by TALENs.

Li Yang, Ya'Nan Liu, Na Zhang, Xiao'Yi Ding, Wei Zhang, Ke'Feng Shen, Liang Huang, Jian'Feng Zhou, Sen Cui, Zun'Min Zhu and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

13 citing papers in PubMed, 28 citations in OpenAlex.

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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

12 authors at 7 institutions in 1 country.

Li YangDepartment of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R.China.
Ya'Nan LiuDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, P.R. China.
Na ZhangDepartment of Hematology, Xijing Hospital Affiliated by The Fourth Military Medical University (FMMU), Xi'an, Shanxi Province, P.R.China.
Xiao'Yi DingDepartment of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R.China.
Wei ZhangDepartment of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R.China.
Ke'Feng ShenDepartment of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R.China.
Liang HuangDepartment of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R.China.
Jian'Feng ZhouDepartment of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R.China.
Sen CuiDepartment of Hematology, Qinghai University Affiliated Hospital, Qinghai University, XiNing, Qinghai Province, P.R.China.
Zun'Min ZhuDepartment of Hematology, Henan Provincial People's Hospital, ZhengZhou, Henan Province, P.R.China.
Zheng HuDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Min XiaoDepartment of Hematology, Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R.China.
Huazhong University of Science and Technology · CNTongji Hospital · CNHenan Provincial People's Hospital · CNQinghai University Affiliated Hospital · CNThe First Affiliated Hospital, Sun Yat-sen University · CNWuhan University · CNXijing Hospital · CN

Funding

1/4 Alcohol Research Consortium in HIV-Administrative Core (ARCH-AC)U24AA020801 · NIAAA · JOHNS HOPKINS UNIVERSITY · PI CHANDER, GEETANJALI, MCCAUL, MARY E · 2011 to 2021
$3.5M
NIAAA NIH HHS U24 AA020801
6 · The paper itself

Abstract

DNA methyltransferase 3A (DNMT3A) mutations occurred in 18%~23% of acute myeloid leukemia (AML) patients, and were considered to be an adverse prognostic factor for adult de novo AML cases. However, the relevant molecular mechanism of the mutation in AML pathogenesis remains obscure. In this study, we established K562 and SKM1 cell model carrying the DNMT3A R882H mutation via transcription activator-like effector nuclease (TALEN) and Clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, and discovered that mutated DNMT3A could promote the proliferative capability of malignant cell clones. Further RNA microarray analysis revealed that some genes crucial for glutathione (GSH) synthesis, including CTH, PSPH, PSAT1 and especially SLC7A11 (the cysteine/glutamate transporter) were significantly up-regulated, which resulted in significant elevation of intracellular GSH levels. A subsequent experiment demonstrated that the mutant clones are resistant to chemotherapy as well as SLC7A11-inhibitorsBy shRNA induced SLC7A11 silencing, we discovered profoundly decreased cellular GSH and cell proliferative ability of DNMT3A mutated clones. Our results provided novel insight into the role of the DNMT3A R882H mutation in AML pathogenesis and suggested that targeting the cellular GSH synthetic pathway could enhance the current therapy for AML patients with the DNMT3A R882H mutation.

Indexed as

MutationAllelesAmino Acid SubstitutionBase SequenceCell ProliferationCell SurvivalComputational BiologyCRISPR-Cas SystemsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Mutational AnalysisDrug Resistance, NeoplasmGene Expression ProfilingGenotypeGlutathioneHumansDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanGlutathioneTranscription Activator-Like Effector NucleasesDNMT3A R882H mutationGSHK562SLC7A11TALENs

Identifiers

PMID28418922
PMCPMC5444751
OpenAlexW2599841336

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.