Differential killing of murine B-cell leukemia (BCL1) by photosensitization with merocyanine 540: implications for autologous bone marrow transplantation.
The efficacy of photosensitization by merocyanine 540 (MC540), a lipophilic fluorescent dye, was investigated in the murine B cell leukemia (BCL1). Normal BALB/c mice were injected with BCL1 cells exposed to MC540, followed by photosensitization with white light for 15 min to 2 h. Mice injected with BCL1 cells exposed for 1 or 2 h showed no sign of leukemia. Lethally irradiated mice were successfully reconstituted with mixtures of syngeneic bone marrow (BM) and BCL1 cells treated with MC540 following exposure to white light. Exposure of BM/BCL1 mixtures for 2 h proved to be effective in purging all BCL1 cells without affecting BM viability, as documented by normal hemopoietic reconstitution of all recipients surviving without evidence of leukemia. All recipients of untreated BM/BCL1 cell mixtures developed leukemia within 42 days. Adoptive transfer of 10(6) spleen cells obtained from treated mice into secondary naive syngeneic recipients was carried out in order to test for dormant BCL1 cells in treated recipients. No leukemia developed in any of the secondary recipients. Previous studies indicate that as few as 10, or possibly less, BCL1 cells are sufficient to cause lethal disease in BALB/c recipients. Our results suggest that MC540 may be an extremely potent tool for in vitro elimination of residual tumor cells while leaving uncommitted progenitor hemopoietic cells intact for hemopoietic reconstitution following lethal marrow ablation.
Mumcuoglu
M
M
Department of Bone Marrow Transplantation and Immunobiology Research, Hadassah University Hospital, Jerusalem, Israel.
Weiss
L
L
Spivak
J
J
Slavin
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D002460:Cell Line; D015448:Leukemia, B-Cell / Q000601:surgery / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010789:Phototherapy; D011744:Pyrimidinones / Q000627:therapeutic use*; D011828:Radiation Chimera; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011744:Pyrimidinones; D011838:Radiation-Sensitizing Agents; C003954:merocyanine dye