Evidence map›Paper›PMID 25122609›Full record

Trial reportBlood2014

Inhibition of sphingosine kinase 2 downregulates the expression of c-Myc and Mcl-1 and induces apoptosis in multiple myeloma.

Jagadish Kummetha Venkata, Ningfei An, Robert Stuart, Luciano J Costa, Houjian Cai, Woodrow Coker, Jin H Song, Kiwana Gibbs, Terri Matson, Elizabeth Garrett-Mayer and 4 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
5.6field-weighted citation impact, top 3% 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.

NCT01410981 completednot on this map

Prognostic Potential of Cell Surface Markers and Pim Kinases in Multiple Myeloma

TypeobservationalSponsorMedical University of South CarolinaRan2011 to 2014Enrolled73ConditionsMultiple Myeloma
NCT02757326 phase1 / phase2terminatednot on this mapstarted 2016, after this paper: background citation

A Phase Ib/II Safety and Efficacy Study of ABC294640 in Patients With Refractory or Relapsed Multiple Myeloma Who Have Previously Been Treated With Proteasome Inhibitors and Immunomodulatory Drugs

TypeinterventionalSponsorRedHill Biopharma LimitedRan2016 to 2019Enrolled13ConditionsMultiple MyelomaArmsOpaganib
3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 96 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Opaganib Protects Against High-Fat Diet-Induced Hypercholesterolemia and Liver Steatosis in Mice.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024
    Article
  12. Article
  13. Lipid metabolic vulnerabilities of multiple myeloma.Clinical and experimental medicine · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

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

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

14 authors at 3 institutions in 1 country.

Jagadish Kummetha Venkata
Ningfei An
Robert Stuart
Luciano J Costa
Houjian Cai
Woodrow Coker
Jin H Song
Kiwana Gibbs
Terri Matson
Elizabeth Garrett-Mayer
Zhuang Wan
Besim Ogretmen
Charles Smith
Yubin Kang
Medical University of South Carolina · USMUSC Hollings Cancer Center · USUniversity of Georgia · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
Plerixafor for allogeneic hematopoietic stem cell transplantationK08HL103780 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI KANG, YUBIN · 2011 to 2015
$649k
NCI NIH HHS P30 CA138313NCI NIH HHS P30CA138313NHLBI NIH HHS K08 HL103780NHLBI NIH HHS K08HL103780
6 · The paper itself

Abstract

Sphingolipid metabolism is being increasingly recognized as a key pathway in regulating cancer cell survival and proliferation. However, very little is known about its role in multiple myeloma (MM). We investigated the potential of targeting sphingosine kinase 2 (SK2) for the treatment of MM. We found that SK2 was overexpressed in MM cell lines and in primary human bone marrow (BM) CD1381 myeloma cells. Inhibition of SK2 by SK2- specific short hairpin RNA or ABC294640 (a SK2 specific inhibitor) effectively inhibited myeloma cell proliferation and induced caspase 3–mediated apoptosis. ABC294640 inhibited primary human CD1381 myeloma cells with the same efficacy as with MM cell lines. ABC294640 effectively induced apoptosis of myeloma cells, even in the presence of BM stromal cells. Furthermore, we found that ABC294640 downregulated the expression of pS6 and directed c-Myc and myeloid cell leukemia 1 (Mcl-1) for proteasome degradation. In addition, ABC294640 increased Noxa gene transcription and protein expression. ABC294640, per se, did not affect the expression of B-cell lymphoma 2 (Bcl-2), but acted synergistically with ABT-737 (a Bcl-2 inhibitor) in inducing myeloma cell death. ABC294640 suppressed myeloma tumor growth in vivo in mouse myeloma xenograft models. Our data demonstrated that SK2 provides a novel therapeutic target for the treatment of MM.This trial was registered at www.clinicaltrials.gov as #NCT01410981.

Indexed as

AdamantaneAnimalsAntineoplastic AgentsApoptosisCaspase 3Cell Line, TumorCell ProliferationDown-RegulationEnzyme InhibitorsHumansMiceMice, Inbred NODMice, KnockoutMice, SCIDMultiple MyelomaMyeloid Cell Leukemia Sequence 1 Protein3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amideAdamantaneAntineoplastic AgentsCASP3 protein, humanCaspase 3Enzyme InhibitorsMCL1 protein, humanMYC protein, humanMyeloid Cell Leukemia Sequence 1 ProteinPhosphotransferases (Alcohol Group Acceptor)PMAIP1 protein, humanProteasome Endopeptidase ComplexProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-mycPyridinesRNA, MessengerRNA, NeoplasmRNA, Small InterferingSphingosine Kinasesphingosine kinase 2, human

Identifiers

PMID25122609
PMCPMC4168346
OpenAlexW2046116275

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.