Relative sensitivity of leukemic (CML) and normal progenitor cells to treatment with the photosensitizer benzoporphyrin derivative and light.
Normal bone marrow and peripheral blood committed progenitor cells were found to be significantly more resistant to treatment with the photosensitizer benzoporphyrin derivative (BPD) and white fluorescent light (11 J/cm2) than were clonogenic cells from two cell lines (K562 and EM2) derived from nonremission patients with myelogenous leukemias. Bone marrow and peripheral blood committed progenitor cells from normal donors were also found to be more resistant to this treatment than were equivalent cells from patients with chronic myelogenous leukemia (CML). Normal bone marrow mononuclear cells grown in long-term marrow culture (LTMC) following treatment with BPD and light showed that no differences in stem cell productivity existed between control and treated samples. When bone marrow from CML patients was treated in the same manner, the numbers of progenitors detected in the nonadherent population during culture were greatly reduced compared to control material. Two rounds of PCR using nested primers to detect BCR-ABL mRNA showed that while this treatment significantly decreased the numbers of stem cells bearing the Philadelphia chromosome, it did not eliminate them.
Jamieson
C
C
University of British Columbia, Vancouver, Canada.
Hornby
A
A
Richter
A
A
Mitchell
D
D
Levy
J
J
D001773:Blood Cells; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005453:Fluorescence; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008027:Light; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D010778:Photochemotherapy; D016133:Polymerase Chain Reaction; D011166:Porphyrins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D011166:Porphyrins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C504224:benzoporphyrin D; D016044:Fusion Proteins, bcr-abl