Interferon-alpha-treated patients with chronic myelogenous leukemia show BCR/ABL-positive peripheral blood progenitor cells surviving long-term culture.
Several groups have shown that Ph-progenitors reappear in LTC of CML bone marrow or PBMNC when the cell preparations were derived from newly diagnosed Ph-positive patients or after induction chemotherapy. We have tested the hypothesis whether LTC may further decrease CML progenitors if the cells to be cultured were from IFN-treated patients. In our experiments, PBMNC were cultured from 7 IFN- and 5 HU-treated patients in stable chronic phase of the disease, and from 9 patients at diagnosis. Progenitor cells in PBMNC were quantitatively analyzed before and after 35 days of LTC by combining the clonogenic assay in semisolid medium with dual-color interphase FISH for identification of the BCR/ABL status of colony-forming progenitor cells. A median of 22 colonies (range 7-88) before and 30 colonies (5-71) after LTC were analyzed per patient. Our results show that the number of BCR/ABL-positive CFC before and after LTC was approximately the same. This was independent of IFN or HU therapy. In the IFN group there were 58% (median) BCR/ABL-positive CFC before and 54% (median) after LTC of PBMNC. In the HU group, 80% of CFC were BCR/ABL-positive before and 85% after LTC. A complete elimination of BCR/ABL-positive cells was not achieved. We conclude that CML early progenitors in PBMNC of IFN-treated CML patients may survive LTC.
Schultheis
B
B
III. Medizinische Universitätsklinik, Klinikum Mannheim, Fakultät für Klinische Medizin der Universität Heidelberg, Germany.
Heissig
B
B
Pasternak
G
G
Hörner
S
S
Hehlmann
R
R
D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D016044:Fusion Proteins, bcr-abl / Q000097:blood*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D017404:In Situ Hybridization, Fluorescence; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D007155:Immunologic Factors; D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl; D006918:Hydroxyurea