benzoporphyrin-d and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

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.

Topics: Blood Cells; Bone Marrow Cells; Colony-Forming Units Assay; Drug Resistance; Drug Screening Assays, Antitumor; Fluorescence; Fusion Proteins, bcr-abl; Hematopoietic Stem Cells; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Light; Neoplastic Stem Cells; Photochemotherapy; Polymerase Chain Reaction; Porphyrins; Radiation Tolerance; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured; Tumor Stem Cell Assay

Benzoporphyrin derivative (BPD) and light is a potent photosensitizer. We investigated this modality as a means to selectively eliminate clonogenic Ph(+) chronic myeloid leukemia (CML) cells. BPD at 10 ng/ml and 10.8 J/cm2 broad spectrum light eliminates from 5 to 6 logs of Ph(+) EM-2 cells. Long-term marrow culture studies of treated mixtures of normal and CML cells indicate that multipotent progenitor cell viability is retained while cells transcribing BCR-ABL are not detected. We conclude that BPD and light may offer a means of providing CML autografts potentially free of Ph(+) clonogenic cells.

Topics: Adult; Base Sequence; Biomarkers, Tumor; Clone Cells; Fusion Proteins, bcr-abl; Hematopoietic Stem Cells; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Sequence Data; Neoplastic Stem Cells; Photochemotherapy; Polymerase Chain Reaction; Porphyrins; Radiation Tolerance; Radiation-Sensitizing Agents; Tumor Cells, Cultured; Tumor Stem Cell Assay