Evidence map›Paper›PMID 26934650›Full record

ArticleOncotarget2016

Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemia.

Haibo Sun, De-Chen Lin, Xiao Guo, Behzad Kharabi Masouleh, Sigal Gery, Qi Cao, Serhan Alkan, Takayuki Ikezoe, Chie Akiba, Ronald Paquette and 6 more

Erratum issuedOpen access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Cell surface GRP78 and the UPR pathway as novel promising therapeutic targets in cancer: an insight into the treatment of acute leukemia by using GRP78-CART cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  17. Contributions of transcriptional noise to leukaemia evolution: KAT2A as a case-study.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  18. The mammalian Ire1 inhibitor, 4µ8C, exhibits broad anti-Frontiers in cellular and infection microbiology · 2024
    Article
  19. Dual RNase activity of IRE1 as a target for anticancer therapies.Journal of cell communication and signaling · 2023
    Review
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 9 institutions in 4 countries.

Haibo SunDepartment of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
De-Chen LinDepartment of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Xiao GuoDepartment of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Behzad Kharabi MasoulehDepartment of Oncology, Hematology and Stem Cell Transplantation, RWTH Aachen University Medical School, Aachen, Germany.
Sigal GeryDepartment of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Qi CaoDepartment of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Serhan AlkanDepartment of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Takayuki IkezoeDepartment of Hematology and Respiratory Medicine, Kochi University, Nankoku, Kochi, Japan.
Chie AkibaDepartment of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ronald PaquetteDepartment of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Wenwen ChienCancer Science Institute of Singapore, National University of Singapore, Singapore.
Carsten Müller-TidowDepartment of Hematology and Oncology, University Hospital Halle, Halle, Germany.
Yang JingDepartment of Hematology and Respiratory Medicine, Kochi University, Nankoku, Kochi, Japan.
Konstantin AgelopoulosDepartment of Medicine, Hematology and Oncology, University of Muenster, Muenster, Germany.
Markus MüschenDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
H Phillip KoefflerDepartment of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cedars-Sinai Medical Center · USKōchi University · JPNational University Cancer Institute, Singapore · SGNational University of Singapore · SGRWTH Aachen University · DEUniversity Hospital in Halle · DEUniversity of California, Los Angeles · USUniversity of California, San Francisco · USUniversity of Münster · DE

Funding

Targeted activation of autoimmune checkpoints in B cell malignanciesR01CA157644 · NCI · YALE UNIVERSITY · PI Markus Müschen · 2011 to 2026
$5.7M
REGULATION OF HEMATOPOIETIC CYTOKINESR01CA026038 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOEFFLER, HAROLD PHILLIP · 1985 to 2013
$4.7M
NCI NIH HHS R01 CA026038NCI NIH HHS R01CA026038-35NCI NIH HHS R01 CA157644
6 · The paper itself

Abstract

Survival of cancer cells relies on the unfolded protein response (UPR) to resist stress triggered by the accumulation of misfolded proteins within the endoplasmic reticulum (ER). The IRE1α-XBP1 pathway, a key branch of the UPR, is activated in many cancers. Here, we show that the expression of both mature and spliced forms of XBP1 (XBP1s) is up-regulated in acute myeloid leukemia (AML) cell lines and AML patient samples. IRE1α RNase inhibitors [MKC-3946, 2-hydroxy-1-naphthaldehyde (HNA), STF-083010 and toyocamycin] blocked XBP1 mRNA splicing and exhibited cytotoxicity against AML cells. IRE1α inhibition induced caspase-dependent apoptosis and G1 cell cycle arrest at least partially by regulation of Bcl-2 family proteins, G1 phase controlling proteins (p21cip1, p27kip1 and cyclin D1), as well as chaperone proteins. Xbp1 deleted murine bone marrow cells were resistant to growth inhibition by IRE1α inhibitors. Combination of HNA with either bortezomib or AS2O3 was synergistic in AML cytotoxicity associated with induction of p-JNK and reduction of p-PI3K and p-MAPK. Inhibition of IRE1α RNase activity increased expression of many miRs in AML cells including miR-34a. Inhibition of miR-34a conferred cellular resistance to HNA. Our results strongly suggest that targeting IRE1α driven pro-survival pathways represent an exciting therapeutic approach for the treatment of AML.

Indexed as

AnimalsEndoribonucleasesHumansLeukemia, Myeloid, AcuteMiceMicroRNAsProtein Kinase InhibitorsProtein Serine-Threonine KinasesRibonucleasesRNA, MessengerSignal TransductionTransfectionUnfolded Protein ResponseUp-RegulationX-Box Binding Protein 1EndoribonucleasesERN1 protein, humanMicroRNAsProtein Kinase InhibitorsProtein Serine-Threonine KinasesRibonucleasesRNA, MessengerX-Box Binding Protein 1XBP1 protein, humanXbp1 protein, mouseER stressIRE1micro RNAunfolded protein responseXBP1

Identifiers

PMID26934650
PMCPMC4951325
OpenAlexW2283921090

What OpenQuestion holds

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LicenceCC BY
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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.