Evidence map›Paper›PMID 27317766›Full record

ArticleOncotarget2016

CCI-007, a novel small molecule with cytotoxic activity against infant leukemia with MLL rearrangements.

Klaartje Somers, Daria A Chudakova, Shiloh M C Middlemiss, Victoria W Wen, Molly Clifton, Alan Kwek, Bing Liu, Chelsea Mayoh, Angelika Bongers, Mawar Karsa and 11 more

Open 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. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. FDA-approved disulfiram as a novel treatment for aggressive leukemia.Journal of molecular medicine (Berlin, Germany) · 2024
    Article
  2. Article
  3. MEIS1 and its potential as a cancer therapeutic target (Review).International journal of molecular medicine · 2021
    Review
  4. Article
  5. Article
  6. SystematicFrontiers in oncology · 2021
    Article
  7. Article
  8. Oncogenic and tumor suppressor function of MEIS and associated factors.Turkish journal of biology = Turk biyoloji dergisi · 2020
    Article
  9. Article
  10. Article
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

21 authors at 4 institutions in 3 countries.

Klaartje SomersChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Daria A ChudakovaChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Shiloh M C MiddlemissChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Victoria W WenChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Molly CliftonChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Alan KwekChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Bing LiuChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Chelsea MayohChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Angelika BongersChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Mawar KarsaChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Sukey PanChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Sarah CruikshankChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Marissa ScandlynChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Wendi HoangChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Toshihiko ImamuraDepartment of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ursula R KeesTelethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
Andrei V GudkovDepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Olga B ChernovaOncotartis, Inc., Buffalo, NY, USA.
Michelle HaberChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Murray D NorrisChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
Michelle J HendersonChildren's Cancer Institute, University of New South Wales, Sydney, New South Wales, Australia.
UNSW Sydney · AUKyoto Prefectural University of Medicine · JPRoswell Park Comprehensive Cancer Center · USThe Kids Research Institute Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There is an urgent need for the development of less toxic, more selective and targeted therapies for infants with leukemia characterized by translocation of the mixed lineage leukemia (MLL) gene. In this study, we performed a cell-based small molecule library screen on an infant MLL-rearranged (MLL-r) cell line, PER-485, in order to identify selective inhibitors for MLL-r leukemia. After screening initial hits for a cytotoxic effect against a panel of 30 cell lines including MLL-r and MLL wild-type (MLL-wt) leukemia, solid tumours and control cells, small molecule CCI-007 was identified as a compound that selectively and significantly decreased the viability of a subset of MLL-r and related leukemia cell lines with CALM-AF10 and SET-NUP214 translocation. CCI-007 induced a rapid caspase-dependent apoptosis with mitochondrial depolarization within twenty-four hours of treatment. CCI-007 altered the characteristic MLL-r gene expression signature in sensitive cells with downregulation of the expression of HOXA9, MEIS1, CMYC and BCL2, important drivers in MLL-r leukemia, within a few hours of treatment. MLL-r leukemia cells that were resistant to the compound were characterised by significantly higher baseline gene expression levels of MEIS1 and BCL2 in comparison to CCI-007 sensitive MLL-r leukemia cells.In conclusion, we have identified CCI-007 as a novel small molecule that displays rapid toxicity towards a subset of MLL-r, CALM-AF10 and SET-NUP214 leukemia cell lines. Our findings suggest an important new avenue in the development of targeted therapies for these deadly diseases and indicate that different therapeutic strategies might be needed for different subtypes of MLL-r leukemia.

Indexed as

Drug Screening Assays, AntitumorAntineoplastic AgentsApoptosisCell Line, TumorDNA-Binding ProteinsGene ExpressionHistone ChaperonesHumansInfantMyeloid-Lymphoid Leukemia ProteinNuclear Pore Complex ProteinsOncogene Proteins, FusionPrecursor Cell Lymphoblastic Leukemia-LymphomaTranscription FactorsAF10-CALM fusion protein, humanAntineoplastic AgentsDNA-Binding ProteinsHistone ChaperonesMyeloid-Lymphoid Leukemia ProteinNuclear Pore Complex ProteinsNUP214 protein, humanOncogene Proteins, FusionSET protein, humanTranscription FactorsapoptosisCALM-AF10 leukemiaHOXA9/MEIS pathwayMLL-rearranged leukemiasmall molecule

Identifiers

PMID27317766
PMCPMC5216782
OpenAlexW2436561939

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.