Evidence map›Paper›PMID 24184354›Full record

ArticleExperimental hematology2014

NPMc+ cooperates with Flt3/ITD mutations to cause acute leukemia recapitulating human disease.

Rachel Rau, Daniel Magoon, Sarah Greenblatt, Li Li, Colleen Annesley, Amy S Duffield, David Huso, Emily McIntyre, John G Clohessy, Markus Reschke and 3 more

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

Article in Experimental hematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-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

25 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Murine Models of Acute Myeloid Leukemia.Frontiers in oncology · 2022
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Mouse Models of Myeloid Malignancies.Cold Spring Harbor perspectives in medicine · 2021
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Knock-in of theOncotarget · 2018
    Article
  18. Review
  19. Article
  20. 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

13 authors at 6 institutions in 1 country.

Rachel RauDepartment of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Electronic address: rerau@bcm.edu.
Daniel MagoonSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sarah GreenblattSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Li LiSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Colleen AnnesleySidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Amy S DuffieldSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David HusoSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emily McIntyreSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
John G ClohessyCancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Markus ReschkeCancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Pier Paolo PandolfiCancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Donald SmallSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Patrick BrownSidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sidney Kimmel Comprehensive Cancer Center · USJohns Hopkins University · USCancer Genetics (United States) · USJohns Hopkins Medicine · USBaylor College of Medicine · USBeth Israel Deaconess Medical Center · US

Funding

THERAPEUTIC USE OF STEM CELLSP01CA070970 · NCI · JOHNS HOPKINS UNIVERSITY · PI SMALL, DONALD · 1998 to 2012
$23.7M
LAB RESEARCH TRAINING IN PEDIATRIC ONCOLOGY-HEMATOLOGYT32CA060441 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN D FRIEDMAN · 1993 to 2026
$14.9M
FLT3 Tyrosine Kinase Inhibitors As Therapy for LeukemiaR01CA090668 · NCI · JOHNS HOPKINS UNIVERSITY · PI SMALL, DONALD · 2002 to 2018
$5.0M
Developing FLT3-Targeted Therapy for Pediatric LeukemiaK23CA111728 · NCI · JOHNS HOPKINS UNIVERSITY · PI BROWN, PATRICK A · 2006 to 2010
$701k
NCI NIH HHS K23 CA111728NCI NIH HHS K23CA111728NCI NIH HHS P01 CA070970NCI NIH HHS P01CA70970NCI NIH HHS R01 CA090668NCI NIH HHS R01CA90668NCI NIH HHS T32 CA060441
6 · The paper itself

Abstract

Cytoplasmic nucleophosmin (NPMc(+)) mutations and FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations are two of the most common known molecular alterations in acute myeloid leukemia (AML); they frequently occur together, suggesting cooperative leukemogenesis. To explore the specific relationship between NPMc+ and FLT3/ITD in vivo, we crossed Flt3/ITD knock-in mice with transgenic NPMc+ mice. Mice with both mutations develop a transplantable leukemia of either myeloid or lymphoid lineage, definitively demonstrating cooperation between Flt3/ITD and NPMc+. In mice with myeloid leukemia, functionally significant loss of heterozygosity of the wild-type Flt3 allele is common, similar to what is observed in human FLT3/ITD+ AML, providing further in vivo evidence of the importance of loss of wild-type FLT3 in leukemic initiation and progression. Additionally, in vitro clonogenic assays reveal that the combination of Flt3/ITD and NPMc+ mutations causes a profound monocytic expansion, in excess of that seen with either mutation alone consistent with the predominance of myelomonocytic phenotype in human FLT3/ITD+/NPMc+ AML. This in vivo model of Flt3/ITD+/NPMc+ leukemia closely recapitulates human disease and will therefore serve as a tool for the investigation of the biology of this common disease entity.

Indexed as

MutationAllelesAnimalsCytoplasmfms-Like Tyrosine Kinase 3Gene DuplicationLeukemia, Myeloid, AcuteLoss of HeterozygosityMiceMice, TransgenicNuclear ProteinsNucleophosminReverse Transcriptase Polymerase Chain ReactionFlt3 protein, mousefms-Like Tyrosine Kinase 3NPM1 protein, humanNuclear ProteinsNucleophosmin

Identifiers

PMID24184354
PMCPMC3932758
OpenAlexW2090932363

What OpenQuestion holds

Textmetadata
LicenceTDM
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.