TY - JOUR
T1 - Establishment of a murine model of aggressive systemic mastocytosis/mast cell leukemia
AU - Demehri, Shadmehr
AU - Corbin, Amie
AU - Loriaux, Marc
AU - Druker, Brian J.
AU - Deininger, Michael W.
N1 - Funding Information:
This work was supported by grants from the Doris Duke Charitable Foundation (B.J.D.), and the Leukemia and Lymphoma Society (B.J.D.). M.W.D. is a Junior Faculty Scholar of the American Society of Hematology.
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.exphem.2005.11.015
DO - 10.1016/j.exphem.2005.11.015
M3 - Article
C2 - 16543062
AN - SCOPUS:33644897314
SN - 0301-472X
VL - 34
SP - 284
EP - 288
JO - Experimental hematology
JF - Experimental hematology
IS - 3
ER -