MPC-1^-CD49e^- immature myeloma cells include CD45^+ subpopulations that can proliferate in response to IL-6 in human myelomas

Using three-colour phenotypic analysis, we detected five subpopulations of myeloma cells (CD38++) in the bone marrow mononuclear cells of human myeloma patients: MPC-1−CD45−CD49e−, MPC-1−CD45+CD49e−, MPC-1+CD45−CD49e−, MPC-1+CD45+CD49e− and MPC-1+CD45+CD49e+. Most of the myeloma cells did not express CD45 but a few MPC-1− immature myeloma cells and some MPC-1+ myeloma cells expressed CD45 and CD45RO but not CD45RA, whereas all of normal early plasma cells in the peripheral blood, lymph node plasma cells and bone marrow plasma cells expressed CD45 and CD45RA, CD45RB but not CD45RO. In order to clarify the biological character of these myeloma subpopulations, we examined the expression of Ki-67 antigen. Proliferating myeloma cells (Ki-67+) were found in the MPC-1− fractions and the MPC-1−CD45+ fractions rather than MPC-1−CD45− fractions. Next, in order to further clarify the biological difference of two immature subpopulations (MPC-1−CD45−CD49e− and MPC-1− CD45+CD49e−), determined cell viability and phenotypic change after culturing with interleukin 6 (IL-6) in vitro. In the presence of IL-6, MPC-1−CD45+ cells kept their viability more than MPC-1−CD45− cells and some MPC-1−CD45− cells could be converted to MPC-1−CD45+ cells. In conclusion, these data suggest that human myeloma cells are phenotypically subdivided into five subpopulations, and among these subpopulations MPC-1−CD45+CD49e− but not MPC-1−CD45−CD49e− immature cells contain proliferating cells in response to IL-6, and IL-6 can also induce expression of CD45 on MPC-1−CD45− subpopulation of immature myeloma cells.