The survival and proliferation of human myeloma cells are considered to be heavily dependent on the microenvironment of bone marrow (BM). This study confirmed that galectin-1 (Gal-1) and SDF-1alpha were produced by bone marrow mononuclear cells of myeloma patients. The addition of Gal-1 and SDF-1alpha to a serum-free synthetic medium, maintained the viability of primary myeloma cells for 2 weeks similar to that before culture. While Gal-1 reduced the viable cell number in CD45RA(+) B cell lines, it maintained the viability of CD45(-) U266 and CD45RA(-)RO(+) ILKM3 myeloma cell lines in the synthetic medium. This was confirmed with the transfection of the PTPRC (CD45) RA, -RB, or -RO gene into CD45(-) U266 cells. The combination of Gal-1 and SDF-1alpha significantly induced phosphorylation of Akt and IkB, while the phosphorylation of ERK1/2 was significantly reduced in CD45RA(+) U266 and Raji cells but not CD45(-) or CD45RA(-) U266 cells. Furthermore, we confirmed that Gal-1 bound to CD45RA in CD45RA(+) Raji cells, and also physically interacted with beta1-integrin by immunoprecipitation followed by Western blotting and confocal microscopy. The results suggest that Gal-1 has two different actions depending on its binding partner, and supports the survival of CD45RA(-) myeloma cells.