Characterization of a unique factor-independent variant derived from human factor-dependent TF-1 cells: a transformed event

Abstract

A factor-independent variant (TF-1a) has been isolated from the factor-dependent TF-1 cell line. The subline has been grown continuously in culture for >1.5 years without added cytokines. The cells retain the ability to respond to multicytokines, with a different response pattern from its parental cell line. The TF-1 cells appeared singly in liquid culture. In contrast, TF-la cells formed aggregates which increased markedly in size and in number upon TGF β1 treatment and showed a diminished TGF β-mediated growth inhibition. TF-la, but not TF-1 cells, formed colonies in soft agar culture in the absence of any added growth factors, and developed the capacity to generate an invasive tumor(s) in nude mice. There was a constitutive activation of MAPK and MEK in TF-la but not in TF-1 cells, which may be one of the mechanisms leading to factor-independent growth of TF-la cells. Phenotypically, TF-1 cells were CD34 +/CD38 +, whereas TF- la cells were CD34 +/CD38 −. This suggests that TF-la may represent a less mature hematopoietic cell than TF-1. In conclusion, TF-1a is different from TF-1 in many important aspects which are associated with neoplastic transformation. The variant appears to be an excellent model for studying the process of progressive malignant transformation of myeloid cells and for studying signal pathways involved in the spontaneous and factor-induced growth of the cells.