| abstract |
The present invention relates to a method for treating a cancer having a protein kinase gene fused to a gene coding for a nuclear-envelop protein or a protein interacting with the nuclear envelop in a subject comprising administering to the subject a therapeutically effective of an arsenic compound, an inductor of type 1 IFNs and a tyrosine kinase inhibitor (TKI), as combined preparation. Indeed, inventors have validated the present invention with in vivo and in vitro models. Treatments started in mice with leukemic burden being >3% (up to 90%) hCD45+CD7+ cells in the blood as detected by flow cytometry in individual tested mice. DASA (20mg/Kg, diluted in 80mM citric acid, pH2.1) was delivered using per os administration. ATO (5mg/Kg, diluted in TBS, pH7) and PolyI:PolyC (PIPC, 20mg/Kg diluted in PBS, SIGMA) were injected using intraperitoneal route. The time scale of drug delivery is indicated for every experiment performed. Mice were weighed every day of treatments, in order to ensure they were not losing too much weight and also to adjust the delivered drug doses. DASA+ATO+PIPC treated mice had a significantly prolonged survival compared to the other treatment conditions, showing major differences between results of treatment protocols. ATO combined with IFN-type 1 inducers and inhibitors of TK represents a powerful way for eradication of T-ALL cells that implicate high ABL1 activity and nuclear pore protein lesions. |