Description
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a distinct subtype of B-ALL with a poor prognosis. Rearrangement of LYN is a recurrent genetic abnormality in Ph-like ALL, but functional analysis of LYN-related fusion genes identified in ALL has not been reported. In this study, we performed functional analysis of the NCOR1-LYN fusion gene identified in a pediatric Ph-like ALL patient to establish its potential for molecular targeted therapy. Retroviral transduction of interleukin (IL)-3-dependent Ba/F3 cells with NCOR1-LYN enabled IL-3-independent proliferation, with constitutive phosphorylation of the tyrosine residues of the LYN kinase domain in the fusion protein. Replacing tyrosine residues with phenylalanine in the LYN kinase domain abolished IL-3 independence. Tyrosine kinase inhibitor dasatinib killed Ba/F3 cells expressing NCOR1-LYN in vitro accompanied by dephosphorylation of the tyrosine residues of the LYN kinase domain in the fusion protein.