In vitro activity of the flt3-inhibitor su5614 and standard cytotoxic agents in tumour cells from patients with wild type and mutated flt3 acute myeloid leukaemia.
The correlation between drug sensitivity in vitro and the mutation status of the FLT3 receptor gene was evaluated in tumour cells from 17 previously untreated AML patients. Tumour cells with internal tandem duplication (ITD) in the FLT3 receptor gene were significantly more sensitive to the FLT3 inhibitor SU5614 than tumour cells with wild type FLT3. Combinations of SU5614 with etoposide and amsacrine showed better effect (p<0.05) compared with the respective single drugs. Our results suggest that the FLT3 inhibitor SU5614 may have a therapeutic potential, especially in combination with other cytotoxic agents, in patients with FLT3-ITD positive AML.
Aleskog
Anna
A
Department of Medical Sciences (Haematology), Uppsala University Hospital, S-75185 Uppsala, Sweden. anna.aleskog@medsci.uu.se
Höglund
Martin
M
Pettersson
Jenny
J
Hermansson
Monica
M
Larsson
Rolf
R
Lindhagen
Elin
E
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D014407:Tumor Cells, Cultured; D051941:fms-Like Tyrosine Kinase 3
D000970:Antineoplastic Agents; D007211:Indoles; D011518:Proto-Oncogene Proteins; C416849:SU 5614; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3