Activating mutations of the FLT3 receptor tyrosine kinase are the most common genetic alteration in acute myeloid leukemia (AML). Here, the transforming potential of newly described, AML-associated FLT3 receptor mutants was demonstrated. Moreover, the sensitivity of different activating FLT3 receptor mutants towards several FLT3 tyrosine kinase inhibitors was investigated. The results indicate that these inhibitors have distinct activities against different mutants.
Furthermore, the role of several FLT3 mutants in vivo was examined using a murine bone marrow transduction/ transplantation model. Mice that received a transplant of FLT3-ITD transduced bone marrow developed a myeloproliferative disease, whereas the tyrosine kinase domain mutants induced a lymphoid disorder in mice.
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Activating mutations of the FLT3 receptor tyrosine kinase are the most common genetic alteration in acute myeloid leukemia (AML). Here, the transforming potential of newly described, AML-associated FLT3 receptor mutants was demonstrated. Moreover, the sensitivity of different activating FLT3 receptor mutants towards several FLT3 tyrosine kinase inhibitors was investigated. The results indicate that these inhibitors have distinct activities against different mutants.
Furthermore, the role of sever...
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