Evidence map›Paper›PMID 37496439›Full record

ArticleHaematologica2024

DNAJC10 maintains survival and self-renewal of leukemia stem cells through PERK branch of the unfolded protein response.

Minjing Li, Xingli Wu, Meiyang Chen, Shiyu Hao, Yue Yu, Xiang Li, Erdi Zhao, Ming Xu, Zhenhai Yu, Zhiqiang Wang and 3 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.9field-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

11 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Minjing LiInstitute of Integrated Medicine, Binzhou Medical University, Yantai 264003.
Xingli WuThe Second School of Clinical Medicine, Binzhou Medical University, Yantai, 264003, China; Laboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Meiyang ChenLaboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Shiyu HaoLaboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Yue YuThe Second School of Clinical Medicine, Binzhou Medical University, Yantai, 264003, China; Laboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Xiang LiThe Second School of Clinical Medicine, Binzhou Medical University, Yantai, 264003, China; Laboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Erdi ZhaoLaboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Ming XuLaboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Zhenhai YuLaboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Zhiqiang WangLaboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003.
Ning XuDepartment of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100.
Changzhu JinLaboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, China; Department of Human Anatomy, School of Basic Medicine, Qilu Medicine University, Zibo, 255300. jinczbmu@126.com.
Yancun YinLaboratory of Experimental Hematology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003. yinyc1985@126.com.
Binzhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Leukemia stem cells (LSC) require frequent adaptation to maintain their self-renewal ability in the face of longer exposure to cell-intrinsic and cell-extrinsic stresses. However, the mechanisms by which LSC maintain their leukemogenic activities, and how individual LSC respond to stress, remain poorly understood. Here, we found that DNAJC10, a member of HSP40 family, was frequently up-regulated in various types of acute myeloid leukemia (AML) and in LSC-enriched cells. Deficiency of DNAJC10 leads to a dramatic increase in the apoptosis of both human leukemia cell lines and LSC-enriched populations. Although DNAJC10 is not required for normal hematopoiesis, deficiency of Dnajc10 significantly abrogated AML development and suppressed self-renewal of LSC in the MLL-AF9-induced murine leukemia model. Mechanistically, inhibition of DNAJC10 specifically induces endoplasmic reticulum stress and promotes activation of PERK-EIF2α-ATF4 branch of unfolded protein response (UPR). Blocking PERK by GSK2606414 (PERKi) or shRNA rescued the loss of function of DNAJC10 both in vitro and in vivo. Importantly, deficiency of DNAJC10 increased sensitivity of AML cells to daunorubicin (DNR) and cytarabine (Ara-C). These data revealed that DNAJC10 functions as an oncogene in MLL-AF9-induced AML via regulation of the PERK branch of the UPR. DNAJC10 may be an ideal therapeutic target for eliminating LSC, and improving the effectiveness of DNR and Ara-C.

Indexed as

Leukemia, Myeloid, AcuteAnimalsCytarabineDaunorubicineIF-2 KinaseHSP40 Heat-Shock ProteinsHumansMiceMolecular ChaperonesStem CellsUnfolded Protein ResponseCytarabineDaunorubicinDNAJC10 protein, humanEIF2AK3 protein, humaneIF-2 KinaseERdj5 protein, mouseHSP40 Heat-Shock ProteinsMolecular Chaperones

Identifiers

PMID37496439
PMCPMC10905105
OpenAlexW4385295344

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.