Evidence map›Paper›PMID 32637030›Full record

ArticleOncotarget2020

RSK inhibitor BI-D1870 inhibits acute myeloid leukemia cell proliferation by targeting mitotic exit.

Hee-Don Chae, Ritika Dutta, Bruce Tiu, Fieke W Hoff, Benedetta Accordi, Valentina Serafin, Minyoung Youn, Min Huang, Nathan Sumarsono, Kara L Davis and 5 more

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

Article in Oncotarget, 2020. 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
2.4field-weighted citation impact, top 9% 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, 31 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Therapeutic targeting of p90 ribosomal S6 kinase.Frontiers in cell and developmental biology · 2023
    Review
  12. CDC20: a novel therapeutic target in cancer.American journal of translational research · 2023
    Review
  13. Article
  14. 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

15 authors at 5 institutions in 3 countries.

Hee-Don ChaeDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Ritika DuttaDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Bruce TiuDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Fieke W HoffDepartment of Pediatric Oncology/Hematology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Benedetta AccordiDepartment of Women's and Children's Health, Onco-Hematology Clinic, University of Padova, Padova, Italy.
Valentina SerafinDepartment of Women's and Children's Health, Onco-Hematology Clinic, University of Padova, Padova, Italy.
Minyoung YounDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Min HuangDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Nathan SumarsonoDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Kara L DavisDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Norman J LacayoDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Martina PigazziDepartment of Women's and Children's Health, Onco-Hematology Clinic, University of Padova, Padova, Italy.
Terzah M HortonTexas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, USA.
Steven M KornblauDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kathleen M SakamotoDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Stanford University · USUniversity of Padua · ITChildren's Cancer Center · USThe University of Texas MD Anderson Cancer Center · USUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The 90 kDa Ribosomal S6 Kinase (RSK) drives cell proliferation and survival in cancers, although its oncogenic mechanism has not been well characterized. Phosphorylated level of RSK (T573) was increased in acute myeloid leukemia (AML) patients and associated with poor survival. To examine the role of RSK in AML, we analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment increased the G2/M population and induced apoptosis in AML cell lines and patient AML cells. Characterization of mitotic phases showed that the metaphase/anaphase transition was significantly inhibited by BI-D1870. BI-D1870 treatment impeded the association of activator CDC20 with APC/C, but increased binding of inhibitor MAD2 to CDC20, preventing mitotic exit. Moreover, the inactivation of spindle assembly checkpoint or MAD2 knockdown released cells from BI-D1870-induced metaphase arrest. Therefore, we investigated whether BI-D1870 potentiates the anti-leukemic activity of vincristine by targeting mitotic exit. Combination treatment of BI-D1870 and vincristine synergistically increased mitotic arrest and apoptosis in acute leukemia cells. These data show that BI-D1870 induces apoptosis of AML cells alone and in combination with vincristine through blocking mitotic exit, providing a novel approach to overcoming vincristine resistance in AML cells.

Indexed as

acute myeloid leukemiaBI-D1870RSKspindle assembly checkpointvincristine

Identifiers

PMID32637030
PMCPMC7321696
OpenAlexW3037121759

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.