RGD Reference Report - The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition. - Rat Genome Database

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The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition.

Authors: Fleischman, AG  Maxson, JE  Luty, SB  Agarwal, A  Royer, LR  Abel, ML  MacManiman, JD  Loriaux, MM  Druker, BJ  Tyner, JW 
Citation: Fleischman AG, etal., Blood. 2013 Nov 21;122(22):3628-31. doi: 10.1182/blood-2013-06-509976. Epub 2013 Sep 30.
RGD ID: 10450482
Pubmed: PMID:24081659   (View Abstract at PubMed)
PMCID: PMC3837511   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2013-06-509976   (Journal Full-text)

We have recently identified targetable mutations in CSF3R (GCSFR) in 60% of chronic neutrophilic leukemia (CNL) and atypical (BCR-ABL-negative) chronic myeloid leukemia (aCML) patients. Here we demonstrate that the most prevalent, activating mutation, CSF3R T618I, is sufficient to drive a lethal myeloproliferative disorder in a murine bone marrow transplantation model. Mice transplanted with CSF3R T618I-expressing hematopoietic cells developed a myeloproliferative disorder characterized by overproduction of granulocytes and granulocytic infiltration of the spleen and liver, which was uniformly fatal. Treatment with the JAK1/2 inhibitor ruxolitinib lowered the white blood count and reduced spleen weight. This demonstrates that activating mutations in CSF3R are sufficient to drive a myeloproliferative disorder resembling aCML and CNL that is sensitive to pharmacologic JAK inhibition. This murine model is an excellent tool for the further study of neutrophilic myeloproliferative neoplasms and implicates the clinical use of JAK inhibitors for this disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CSF3RHumanchronic neutrophilic leukemia  IMP  RGD 
Csf3rRatchronic neutrophilic leukemia  ISOCSF3R (Homo sapiens) RGD 
Csf3rMousechronic neutrophilic leukemia  ISOCSF3R (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Csf3r  (colony stimulating factor 3 receptor)

Genes (Mus musculus)
Csf3r  (colony stimulating factor 3 receptor)

Genes (Homo sapiens)
CSF3R  (colony stimulating factor 3 receptor)


Additional Information