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Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones.

Cancer cell | 2018

Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.

Pubmed ID: 30245083 RIS Download

Additional research tools detected in this publication

Antibodies used in this publication

Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MR/M009157/1

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This is a list of tools and resources that we have found mentioned in this publication.


Bowtie (tool)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

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Microsoft Excel (tool)

RRID:SCR_016137

Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.

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Rabbit IgG Control Antibody, Unconjugated (antibody)

RRID:AB_1163661

This unknown targets Rabbit IgG Control

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CD 25, Interleukin-2 Receptor alpha chain (antibody)

RRID:AB_563538

This monoclonal targets Prokaryotic recombninant protein corresponding to external domain

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CD56 (antibody)

RRID:AB_2732847

This monoclonal targets CD56

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CD34 (antibody)

RRID:AB_10563908

This monoclonal targets CD34

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PE anti-human CD366 (Tim-3) (antibody)

RRID:AB_2116576

This monoclonal targets CD366

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PE anti-human/mouse CD49f (antibody)

RRID:AB_893373

This monoclonal targets CD49f

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PE/Cyanine7 anti-human CD123 (antibody)

RRID:AB_493576

This monoclonal targets CD123

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PE anti-human CD45RA (antibody)

RRID:AB_314412

This monoclonal targets CD45RA

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PE anti-human CD99 (antibody)

RRID:AB_2616974

This monoclonal targets CD99

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PE anti-human CD97 (antibody)

RRID:AB_2076182

This monoclonal targets CD97

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PE anti-human CD82 (antibody)

RRID:AB_1595455

This monoclonal targets CD82

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PE anti-human CD25 (antibody)

RRID:AB_314276

This monoclonal targets CD25

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Human JAM-C Phycoerythrin MAb (Clone 208212) (antibody)

RRID:AB_2128938

This monoclonal targets Human JAM-C Phycoerythrin MAb (Clone 208212)

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Human IL-1 RAcP/IL-1 R3 Phycoerythrin MAb (Cl 89412) (antibody)

RRID:AB_10717521

This monoclonal targets Human IL-1 RAcP/IL-1 R3 Phycoerythrin MAb (Cl 89412)

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Human MICL Phycoerythrin MAb (Cl 687317) (antibody)

RRID:AB_10892515

This monoclonal targets Human MICL Phycoerythrin MAb (Cl 687317)

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Human MMR/CD206 Phycoerythrin MAb (Clone 685641) (antibody)

RRID:AB_10889015

This monoclonal targets Human MMR/CD206 Phycoerythrin MAb (Clone 685641)

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Human CD200 Phycoerythrin MAb (Clone 325516) (antibody)

RRID:AB_1061611

This monoclonal targets Human CD200 Phycoerythrin MAb (Clone 325516)

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CorelDRAW Graphics Suite (software resource)

RRID:SCR_014235

Graphic design software which can be used for vector illustration and page layout, web design, and photo editing. Features include: search, preview, application and transformation capabilities for both vector pattern and bitmap pattern fills; a fill engine with complete control over fountain, bitmap pattern and vector pattern fills; templates for website design; and vector shaping and page layout tools.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Gene Set Enrichment Analysis (software resource)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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DAVID (software resource)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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MACS (software resource)

RRID:SCR_013291

Software Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.

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Bowtie 2 (software resource)

RRID:SCR_016368

Ultrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.

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HOMER (software resource)

RRID:SCR_010881

Software tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.

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FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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MaxQuant (software resource)

RRID:SCR_014485

A quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.

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MS-5 [Mouse bone marrow] (cell line)

RRID:CVCL_2128

Cell line MS-5 [Mouse bone marrow] is a Stromal cell line with a species of origin Mus musculus

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