Does long-term culture favor normal clonogenic cells from interferon-treated patients with chronic myelogenous leukemia?

We have tested whether peripheral blood mononuclear cells (PBMNCs) from int erferon (IFN)-treated patients may lose residual BCR-ABL sequence-positive progenitor cells when long-term cultured for 35 days on allogeneic stromal cells. IFN-treated patients have low white blood cell counts and a fair num ber of BCR-ABL-negative colony-forming cells in the peripheral blood. Parti cularly, IFN responders show increased numbers of normal hematopoietic cell s. We have quantitatively analyzed progenitor cells in PBMNCs of IFN-treate d patients by combining the clonogenic assay in semisolid medium with inter phase fluorescent in site hybridization (FISH). Thus, the identification is possible of the BCR-ABL status of colony-forming progenitor cells. In IFN- treated patients, the number of BCR-ABL-positive CFCs is considerably decre ased and BCR-ABL-negative CFCs appear in the peripheral blood. We could sho w that after LTC for 35 days of the same PBMNCs on irradiated allogeneic no rmal stromal cells residual BCR-ABL sequence-positive CFCs were still prese nt. In some cases the relative number of BCR-ABL sequence-positive CFCs was found to be increased after LTC. A minor proportion of blood samples from IFN-treated patients did not give rise to CFCs after LTC on allogeneic stro mal cells (three of 10 patients). Inter- and intraindividual variations can be found with regard to loss or gain of BCR-ABL sequence-positive colonies after LTC. We conclude that early CML progenitor cells persist in the peri pheral blood of IFN-treated patients and that a certain proportion may surv ive long-term culture.