Differential Effects of Melphalan on Mouse Myeloma (Adj. PC-5) and Hemopoietic Stem Cells1

The effect of melphalan on mouse myeloma and hemopoietic progenitor cells was studied with a primary cell culture assay for mouse myeloma stem cells developed by Park, Bergsagel, and McCulloch and bone marrow cell culture and spleen colony assays for hemopoietic progenitor cells. Myeloma and bone marrow cells were exposed in vivo to graded doses of melphalan and harvested 3 and 24 hr later for assays of the surviving fractions. The sensitivity of myeloma cells was more than 70 times greater than that of normal bone marrow cells. Exposure of the 2 cell classes to melphalan in culture also showed a similar differential effect of melphalan. The sensitivity of normal and regenerating bone marrow to melphalan was almost identical when assayed by cell culture or the spleen colony method. These results indicate that the sensitivity of hemopoietic progenitor cells to melphalan is not influenced by the proliferative state of these cells. It would appear that the vast difference in the sensitivity of these 2 cell classes to melphalan is dependent on intrinsic differences between myeloma stem cells and hemopoietic progenitor cells.