Growth-factor-independent proliferation in vitro and tumorigenicity in vivo are associated in basophil/mast-cell lines and their somatic hybrids

Abstract

According to a current model, leukemic cells arise from normal hemopoietic progenitors as a result of two phenotypic changes: (1) a shift from a high to a low probability of completing differentiation, and (2) the loss of requirement for physiological growth regulators, such as multilineage hemopoietic growth factor (MHGF). In agreement with this model, we have recently reported that the spontaneous, in vitro, malignant transformation of a factor-dependent basophil/mast-cell line was coincidental with the appearance of MHGF-independent proliferation in vitro. We have now fused the MHGF-independent cells with their nontransformed counterparts. In the present study, 29 out of 32 hybrid clones analyzed exhibited an association between, on the one hand, the absence of MHGF requirement in vitro and high tumorigenicity in vivo and, on the other hand, MHGF-dependent proliferation in vitro and a reduced capacity to make tumors in vivo. These data support the idea that the tumorigenic behavior of the transformed cells in vivo and their lack of requirement for MHGF in vitro are directly related.