Evidence map›Paper›PMID 25450514›Full record

ArticleExperimental hematology2015

Variegated clonality and rapid emergence of new molecular lesions in xenografts of acute lymphoblastic leukemia are associated with drug resistance.

Daniel Nowak, Natalia L M Liem, Maximilian Mossner, Marion Klaumünzer, Rachael A Papa, Verena Nowak, Johann C Jann, Tadayuki Akagi, Norihiko Kawamata, Ryoko Okamoto and 8 more

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

Article in Experimental hematology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.9field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 22 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

18 authors at 8 institutions in 5 countries.

Daniel NowakDivision of Hematology and Oncology, Cedars Sinai Medical Center, University of California, Los Angeles, School of Medicine, Los Angeles, CA, United States; Department of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany. Electronic address: daniel.nowak@medma.uni-heidelberg.de.
Natalia L M LiemChildren's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia.
Maximilian MossnerDepartment of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany.
Marion KlaumünzerDepartment of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany.
Rachael A PapaChildren's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia.
Verena NowakDivision of Hematology and Oncology, Cedars Sinai Medical Center, University of California, Los Angeles, School of Medicine, Los Angeles, CA, United States; Department of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany.
Johann C JannDepartment of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany.
Tadayuki AkagiDepartment of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
Norihiko KawamataDivision of Hematology and Oncology, Cedars Sinai Medical Center, University of California, Los Angeles, School of Medicine, Los Angeles, CA, United States.
Ryoko OkamotoDivision of Hematology and Oncology, Cedars Sinai Medical Center, University of California, Los Angeles, School of Medicine, Los Angeles, CA, United States.
Nils H ThoennissenDivision of Hematology and Oncology, Cedars Sinai Medical Center, University of California, Los Angeles, School of Medicine, Los Angeles, CA, United States.
Motohiro KatoDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Masashi SanadaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Wolf-Karsten HofmannDepartment of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany.
Seishi OgawaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Glenn M MarshallKids Cancer Centre, Sydney Children's Hospital, Randwick, Australia.
Richard B LockChildren's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia.
H Phillip KoefflerDivision of Hematology and Oncology, Cedars Sinai Medical Center, University of California, Los Angeles, School of Medicine, Los Angeles, CA, United States; National University of Singapore, Singapore, Singapore.
Cedars-Sinai Medical Center · USHeidelberg University · DEKyoto University · JPUNSW Sydney · AUUniversity Hospital Heidelberg · DEUniversity of California, Los Angeles · USKanazawa University · JPSydney Children's Hospital · AU

Funding

REGULATION OF HEMATOPOIETIC CYTOKINESR01CA026038 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOEFFLER, HAROLD PHILLIP · 1985 to 2013
$4.7M
NCI NIH HHS 5R01CA026038-35NCI NIH HHS R01 CA026038
6 · The paper itself

Abstract

The use of genome-wide copy-number analysis and massive parallel sequencing has revolutionized the understanding of the clonal architecture of pediatric acute lymphoblastic leukemia (ALL) by demonstrating that this disease is composed of highly variable clonal ancestries following the rules of Darwinian selection. The current study aimed to analyze the molecular composition of childhood ALL biopsies and patient-derived xenografts with particular emphasis on mechanisms associated with acquired chemoresistance. Genomic DNA from seven primary pediatric ALL patient samples, 29 serially passaged xenografts, and six in vivo selected chemoresistant xenografts were analyzed with 250K single-nucleotide polymorphism arrays. Copy-number analysis of non-drug-selected xenografts confirmed a highly variable molecular pattern of variegated subclones. Whereas primary patient samples from initial diagnosis displayed a mean of 5.7 copy-number alterations per sample, serially passaged xenografts contained a mean of 8.2 and chemoresistant xenografts a mean of 10.5 copy-number alterations per sample, respectively. Resistance to cytarabine was explained by a new homozygous deletion of the DCK gene, whereas methotrexate resistance was associated with monoallelic deletion of FPGS and mutation of the remaining allele. This study demonstrates that selecting for chemoresistance in xenografted human ALL cells can reveal novel mechanisms associated with drug resistance.

Indexed as

AnimalsAntineoplastic AgentsBiopsyClone CellsCytarabineDeoxycytidine KinaseDexamethasoneDisease ProgressionDNA, NeoplasmDrug Resistance, NeoplasmFemaleGene DosageHeterograftsHumansMaleMethotrexateAntineoplastic AgentsCytarabineDeoxycytidine KinaseDexamethasoneDNA, Neoplasmfolylpolyglutamate synthetaseMethotrexateNeoplasm ProteinsPeptide SynthasesVincristine

Identifiers

PMID25450514
PMCPMC5894481
OpenAlexW2021428141

What OpenQuestion holds

Textmetadata
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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.