c-Kit/D816V Stable Ba/F3 Cell Line

c-Kit or stem cell factor (SCF) receptor is a type III tyrosine kinase receptor that has a major role in the hematopoietic system. Gain-of-function mutations of the receptor have been observed in malignancies such as myeloid leukemia, gastrointestinal stromal tumors, and testicular carcinoma. While loss-of-function mutations were found in defects relating to hematopoiesis, melanogenesis, and gametogenesis. c-Kit/D816V-Stable Ba/F3 cells (with GNNK- isoform) has D-to-V mutation at position 816, a common c-Kit mutation where there is a substitution of the aspartic acid residue at position 816 to a valine; resulting in receptor activation independent from the Src family kinase phosphorylation and ubiquitination. It has lower surface c-kit receptor expression and downstream biological responses compared to wild-type c-Kit. The GNNK- isoform is the outcome of the c-Kit gene alternative splicing sites, resulting in different isoforms of the tetrapeptide GNNK and is the main transcript found in human malignancies. The cells are resistant to Imatinib (Gleevec), an inhibitor of the c-Kit juxtamembrane mutations, and are able to proliferate in the absence of the ligand SCF. The analogous mutations are closely related to tyrosine kinase Flt3 mutated at aspartic acid 835 found in acute myeloid leukemia patients. Together with the wild-type c-Kit stable Ba/F3 cells (Cat. No. T3041 and T3042), these cell lines are suitable for studies in drug discovery for mutations in the c-Kit receptor which are associated to oncogenic and other diseases.