Establishment of a murine model of aggressive systemic mastocytosis/mast cell leukemia

Shadmehr Demehri, Amie Corbin, Marc Loriaux, Brian Druker, Michael W. Deininger

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL) are rare but devastating diseases, for which no effective specific therapy is currently available. Most patients harbor the D816V mutant of KIT (KIT D816V), a constitutively active tyrosine kinase that is essential for pathogenesis, raising hopes that specific inhibition of KITD816V may be therapeutically efficacious. To facilitate testing of new inhibitors in an animal model with similarity to human ASM/MCL, we developed a murine model that is based on retro-orbital injection of P815 cells, a murine mastocytoma line expressing the homologous D814Y mutant of KIT, into syngeneic DBA/2 mice. We found that the systemic disease induced by this approach is highly reproducible and resembles human ASM/MCL. Malignant mast cells were consistently detected in the peripheral blood by morphology and fluorescence-activated cell sorting after a stable latency whose length could be modulated by inoculum size. This easy and inexpensive tumor model should be useful for testing potential drugs with activity against KITD816V.

Original languageEnglish (US)
Pages (from-to)284-288
Number of pages5
JournalExperimental Hematology
Volume34
Issue number3
DOIs
StatePublished - Mar 2006

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Mast-Cell Leukemia
Systemic Mastocytosis
Mastocytoma
Inbred DBA Mouse
Rare Diseases
Mast Cells
Protein-Tyrosine Kinases
Flow Cytometry
Animal Models
Injections
Pharmaceutical Preparations
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Establishment of a murine model of aggressive systemic mastocytosis/mast cell leukemia. / Demehri, Shadmehr; Corbin, Amie; Loriaux, Marc; Druker, Brian; Deininger, Michael W.

In: Experimental Hematology, Vol. 34, No. 3, 03.2006, p. 284-288.

Research output: Contribution to journalArticle

Demehri, Shadmehr ; Corbin, Amie ; Loriaux, Marc ; Druker, Brian ; Deininger, Michael W. / Establishment of a murine model of aggressive systemic mastocytosis/mast cell leukemia. In: Experimental Hematology. 2006 ; Vol. 34, No. 3. pp. 284-288.
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