Evidence map›Paper›PMID 25116387›Full record

ArticleScientific reports2014

Using RNA-seq and targeted nucleases to identify mechanisms of drug resistance in acute myeloid leukemia.

Susan K Rathe, Branden S Moriarity, Christopher B Stoltenberg, Morito Kurata, Natalie K Aumann, Eric P Rahrmann, Natashay J Bailey, Ellen G Melrose, Dominic A Beckmann, Chase R Liska and 1 more

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

Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

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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

11 authors at 2 institutions in 1 country.

Susan K RatheMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Branden S Moriarity1] Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA [3] Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
Christopher B StoltenbergMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Morito KurataMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Natalie K AumannMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Eric P Rahrmann1] Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA [3] Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
Natashay J BaileyMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Ellen G MelroseMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Dominic A Beckmann1] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA [2] Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
Chase R LiskaMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
David A Largaespada1] Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA [2] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA [3] Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA [4] Brain Tumor Program, University of Minnesota, Minneapolis, MN, USA [5] Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
University of Minnesota Medical Center · USUniversity of Minnesota · US

Funding

TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
NCI NIH HHS T32 CA009138
6 · The paper itself

Abstract

The evolution from microarrays to transcriptome deep-sequencing (RNA-seq) and from RNA interference to gene knockouts using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and Transcription Activator-Like Effector Nucleases (TALENs) has provided a new experimental partnership for identifying and quantifying the effects of gene changes on drug resistance. Here we describe the results from deep-sequencing of RNA derived from two cytarabine (Ara-C) resistance acute myeloid leukemia (AML) cell lines, and present CRISPR and TALEN based methods for accomplishing complete gene knockout (KO) in AML cells. We found protein modifying loss-of-function mutations in Dck in both Ara-C resistant cell lines. CRISPR and TALEN-based KO of Dck dramatically increased the IC₅₀ of Ara-C and introduction of a DCK overexpression vector into Dck KO clones resulted in a significant increase in Ara-C sensitivity. This effort demonstrates the power of using transcriptome analysis and CRISPR/TALEN-based KOs to identify and verify genes associated with drug resistance.

Indexed as

3T3 CellsAnimalsAntimetabolites, AntineoplasticBase SequenceCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCytarabineDrug Resistance, NeoplasmHigh-Throughput Nucleotide SequencingLeukemia, Myeloid, AcuteMiceProtein Serine-Threonine KinasesRNA InterferenceRNA, Small InterferingSequence Analysis, RNAAntimetabolites, AntineoplasticCytarabineProtein Serine-Threonine KinasesRNA, Small Interfering

Identifiers

PMID25116387
PMCPMC4131221
OpenAlexW2053886270

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.