CHARACTERIZATION OF A UNIQUE FACTOR-INDEPENDENT VARIANT DERIVED FROM HUMAN FACTOR-DEPENDENT TF-1 CELLS - A TRANSFORMED EVENT

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 patter n from its parental cell line. The TF-1 cells appeared singly in liqui d culture. In contrast, TF-1a cells formed aggregates which increased markedly in size and in number upon TGF beta 1 treatment and showed a diminished TGF beta-mediated growth inhibition. TF-1a, but not TF-1 ce lls, formed colonies in soft agar culture in the absence of any added growth factors, and developed the capacity to generate an invasive tum or(s) in nude mice. There was a constitutive activation of MAPK and ME K in TF-1a but not in TF-1 cells, which may be one of the mechanisms l eading to factor-independent growth of TF-1a cells. Phenotypically, TF -1 cells were CD34(+) /CD38(+), whereas TF-1a cells were CD34(+)/CD38( -). This suggests that TF-1a may represent a less mature hematopoietic cell than TF-1. In conclusion, TF-la is different from TF-1 in many i mportant 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 study ing signal pathways involved in the spontaneous and factor-induced gro wth of the cells. (C) 1998 Elsevier Science Ltd. All rights reserved.