Evidence map›Paper›PMID 25365263›Full record

ArticleOncotarget2014

Preclinical efficacy of maternal embryonic leucine-zipper kinase (MELK) inhibition in acute myeloid leukemia.

Houda Alachkar, Martin B G Mutonga, Klaus H Metzeler, Noreen Fulton, Gregory Malnassy, Tobias Herold, Karsten Spiekermann, Stefan K Bohlander, Wolfgang Hiddemann, Yo Matsuo and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

41 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
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  3. Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review
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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 5 institutions in 4 countries.

Houda AlachkarDepartment of Medicine, University of Chicago, Chicago, IL.
Martin B G MutongaDepartment of Medicine, University of Chicago, Chicago, IL.
Klaus H MetzelerDepartment of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany. Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, München, Germany.
Noreen FultonDepartment of Medicine, University of Chicago, Chicago, IL.
Gregory MalnassyDepartment of Medicine, University of Chicago, Chicago, IL.
Tobias HeroldDepartment of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany. Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, München, Germany.
Karsten SpiekermannDepartment of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany. Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, München, Germany.
Stefan K BohlanderDepartment of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand.
Wolfgang HiddemannDepartment of Internal Medicine 3, University Hospital Grosshadern, Ludwig-Maximilians-Universität (LMU), München, Germany. Clinical Cooperative Group Leukemia, Helmholtz Center Munich for Environmental Health, München, Germany.
Yo MatsuoOncoTherapy Science, Inc., Kanagawa, Japan.
Wendy StockDepartment of Medicine, University of Chicago, Chicago, IL.
Yusuke NakamuraDepartment of Medicine, University of Chicago, Chicago, IL.
University of Chicago · USHelmholtz Zentrum München · DELudwig-Maximilians-Universität München · DEOncoTherapy Science (Japan) · JPUniversity of Auckland · NZ

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI MARK W. LINGEN · 1985 to 2026
$122.1M
Experimental Therapeutics: Clinical Trials Network with Phase I EmphasisUM1CA186705 · NCI · UNIVERSITY OF CHICAGO · PI MAITLAND, MICHAEL L., RATAIN, MARK J · 2014 to 2015
$987k
NCI NIH HHS P30 CA014599NCI NIH HHS P30 CA14599-36NCI NIH HHS UM1 CA186705
6 · The paper itself

Abstract

Maternal embryonic leucine-zipper kinase (MELK), which was reported to be frequently up-regulated in various types of solid cancer, plays critical roles in formation and maintenance of cancer stem cells. However, little is known about the relevance of this kinase in hematologic malignancies. Here we report characterization of possible roles of MELK in acute myeloid leukemia (AML). MELK is expressed in AML cell lines and AML blasts with higher levels in less differentiated cells. MELK is frequently upregulated in AML with complex karyotypes and is associated with worse clinical outcome. MELK knockdown resulted in growth inhibition and apoptosis of leukemic cells. Hence, we investigated the potent anti-leukemia activity of OTS167, a small molecule MELK kinase inhibitor, in AML, and found that the compound induced cell differentiation and apoptosis as well as decreased migration of AML cells. MELK expression was positively correlated with the expression of FOXM1 as well as its downstream target genes. Furthermore, MELK inhibition resulted in downregulation of FOXM1 activity and the expression of its downstream targets. Taken together, and given that OTS167 is undergoing a phase I clinical trial in solid cancer, our study warrants clinical evaluation of this compound as a novel targeted therapy for AML patients.

Indexed as

AdolescentAdultApoptosisBlotting, WesternCell CycleCell Line, TumorEnzyme InhibitorsFemaleFlow CytometryFluorescent Antibody TechniqueHumansKaplan-Meier EstimateLeukemia, Myeloid, AcuteMaleMiddle AgedOligonucleotide Array Sequence AnalysisEnzyme InhibitorsMELK protein, humanProtein Serine-Threonine Kinases

Identifiers

PMID25365263
PMCPMC4323011
OpenAlexW2163976460

What OpenQuestion holds

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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.