Heterogeneity of peripheral blood T-cell colony-forming cells in patients with T-cell malignancies

Some peripheral blood clonogenic T-cells from patients with T-cell malignancies can generate colonies in methylcellulose in the absence of added growth factors or mitogen stimulation (T-CFCs). T-CFC from these patients were also able to form colonies in semi-solid media in the presence of added growth factors (T-CFCi). T-CFCs, in contrast to T-CFCi, were highly clonogenic cells possessing self-renewal capacity in the absence of added growth factors. T-CFCs were in cell cycle and more sensitive to Ara-C or ADM (D10 = 0.009 and 0.025 microgram/ml respectively than T-CFCi (D10 = 1 and 2 micrograms/ml respectively). Furthermore, T-CFCs were more radiosensitive (Do less than 1.1 Gy) than T-CFCi (Do less than 5 Gy). T-cell precursors from patients with immature blast cells (E-, OKT3-, OKT6+, OKT10+) were independent of added growth factors for their in vitro proliferation whereas in cases with mature blast cells (E+, OKT3+) T-CFC were significantly more dependent. These observations strongly suggest that T-CFCs and T-CFCi represent different cell subsets. The phenotype of pooled induced and spontaneous T-cell colonies was highly individualized. However, colonies contained a significant proportion of relatively immature T-cells as assessed by the proportion of OKT6+, OKT10+, OKT3+ and E+ cells. The phenotype of colony cells was quite similar to that observed on fresh leukemic cells suggesting a defect of the in vitro differentiation of both T-CFCs and T-CFCi.