Limiting dilution analysis for detection of residual leukemic cells after bone marrow combined decontamination with mafosfamide followed by merocyanine-540-mediated photosensitization

Int J Cell Cloning. 1989 Jul;7(4):223-31. doi: 10.1002/stem.5530070404.

Abstract

Human acute myelogenous or lymphoblastic leukemia cells of the K-562 and CCRF-SB lines were mixed with an excess of normal human bone marrow cells to simulate a leukemia remission marrow. The cell mixtures were then incubated in vitro with mafosfamide (AZ) followed by the photoreactive dye merocyanine-540 (MC). Treated cells (1 x 10(4] were seeded in microwell plates, and increasing numbers of the line used to contaminate the normal marrow were added. Treatment with AZ alone produced total elimination (i.e., 6 logs) of CCRF-SB cells, while addition of merocyanine-540 increased the cloning efficiency from 22% to 24.4%. After treatment of the K-562-contaminated cell mixtures with AZ, nearly 1.6 logs of K-562 acute myelogenous blasts were still present, whereas AZ purging followed by MC-mediated photosensitization resulted in 100% elimination of clonogenic cells. Moreover, the combined treatment caused an increase of the cloning efficiency from 37.3% to 62%, clearly indicating that cleansing by the two agents combined was more effective than treatment with one agent alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Bone Marrow / drug effects*
  • Bone Marrow / pathology
  • Cell Line
  • Colony-Forming Units Assay*
  • Cyclophosphamide / analogs & derivatives*
  • Cyclophosphamide / pharmacology
  • Dye Dilution Technique*
  • Humans
  • Leukemia / pathology*
  • Light*
  • Pyrimidinones / pharmacology*
  • Radiation-Sensitizing Agents / pharmacology*
  • Tumor Stem Cell Assay*

Substances

  • Antineoplastic Agents
  • Pyrimidinones
  • Radiation-Sensitizing Agents
  • merocyanine dye
  • mafosfamide
  • Cyclophosphamide