Conditional tpm3-alk transgenic mice

TPM3-ALK (Tropomyosin 3-Anaplastic lymphoma kinase) is oncogenic tyrosine kinase implicated in the pathogenesis of human ALK-positive lymphoma. We have developed novel conditional mouse models for ALK-induced lymphomagenesis, by using the tetracycline regulatory system under the control of the EmuSRalpha enhancer/promoter. The expression of oncogene resulted in the arrest of the differentiation of early B-cells and lymphomagenesis associated with skin keratoacanthoma lesions, likely due to aberrant ALK expression in keratinocytes. The inactivation of the ALK oncogene upon doxycycline or the specific ALK inhibitor (PF-2341066)treatment was sufficient to induce sustained regression of both hematopoietic tumors and skin disease, illustrating the value of these mouse models for the validation of ALK tyrosine kinase inhibitors.

Interest / Relevance: Our model offer a new tool to investigate, in vivo, the molecular mechanisms associated with ALK-induced lymphoproliferative disorders.
- To assess the mechanism of tyrosine kinase fusion oncoprotein positive tumor development
- To validate in vivo and in vitro the efficiency of specific ALK inhibitors
- To assess tumour growth inhibition upon chemical ALK inactivation
Keywords: ALK tyrosine kinase oncoprotein , B-lymphoma , skin hyperplasia , targeted therapy , lymphoma regression
Publications:
Giuriato S Foisseau M Dejean E Felsher DW Al Saati T Demur C Ragab A Kruczynski A Schiff C Delsol G Meggetto F. Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B-cell lymphoma/leukemia. Blood. 2010 May 20;115(20):4061-70. doi: 10.1182/blood-2008-06-163386. Epub 2010 Mar 11.

Reference:

RT00401

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Fabienne MEGGETTO-PRADELLE
Inserm Transfert
Research Tools
Species: mouse
Genotype: heterozygote
Strain: FVB/N
Genetic Background: FVB/N
Applications: ALK tyrosine kinase fusion oncoprotein-induced lymphomagenesis
Last update: 05/12/2019

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