GROWTH MODULATION OF HUMAN LEUKEMIC, PRELEUKEMIC, AND MYELOMA PROGENITOR CELLS BY L-ASCORBIC-ACID

L-Ascorbic acid (LAA) was shown to modulate the in vitro growth of colonies of human and mouse myeloma progenitor-stem cells through use of a unique cell-culture assay. LAA was also shown to modulate the in vitro growth of leukemic colony-forming cells (L-CFC) from bone marrow of patients with acute myelocytic leukemia. LAA enhanced the growth of L-CFC in 35% of patients and suppressed the growth of L-CFC in 15% of patients. The minimum effective concentration was 0.03 mmol/L. The modulating effect is specific to LAA because other redox compounds are without effect. From the cell kinetic standpoint, the LAA effect is cytostatic rather than cytocidal. Similar LAA effects have prognostic value in patients with myelodysplastic syndromes (MDS), with LAA-sensitive patients displaying shorter survival than LAA-insensitive patients. MDS appears to be the ideal disease for clinical trials involving in vivo LAA manipulation to control the disease process.