Transformation, inhibition, and signaling properties of the fusion tyrosine kinase formed by RNA binding motif 6 (RBM6) and colony-stimulating factor 1 receptor (CSF1R). (A) The retroviral constructs used in the study. MSCV indicates murine stem cell virus; Neo, Neomycin; and LTR, long terminal repeat. (B) BaF3 cells retrovirally transduced with these constructs were grown in the absence of IL-3 after selecting with 1 mg/mL G418 for 7 days. (C) Detection of RBM6-CSF1R and its truncation in BaF3 cells after 3 hours of IL-3 withdrawal, accompanied by phosphorylation of STAT5. ▶ indicates full-length CSF1R; *, nonspecific band; ▶▶, cytoplasmic domain of CSF1R; and →, RBM6-CSF1R and CSF1R (trunc). (D) Dose-response graph of imatinib for BaF3 cells expressing RBM6-CSF1R and its N-terminal truncation. BaF3/BCR-ABL, FLT3-ITD, as well as MKPL-1 were used as controls. (E) BaF3 cells established as in panel B were injected subcutaneously into Balb/cnu/nu mice. Mice were monitored daily for tumor formation and size and were killed when tumors reached 2 cm × 2 cm.
