DIVERSE EFFECTS OF ANTI-CD44 ANTIBODIES ON THE STROMAL CELL-MEDIATED SUPPORT OF NORMAL BUT NOT LEUKEMIC (CML) HEMATOPOIESIS IN-VITRO

We have identified three non-cross-reacting antihuman CD44 monoclonal antibodies that have significant positive or negative (or no) effects on normal human haemopoiesis in the long-term culture (LTC) system. Th ese effects manifested as increases or decreases in the number of LTC- initiating cells (LTC-IC), and the number of colony-forming cells (CFC ) recovered from cultures in which either unseparated or highly purifi ed CD34(+)CD38(-) normal marrow cells were placed on pre-established n ormal marrow feeder layers in the presence or absence of each antibody . The effects seen were rapid and sustained, and dependent on the pres ence of a preformed feeder layer. Interestingly, the same anti-CD44 an tibodies had no effect on the maintenance of leukaemic (Ph+) progenito rs (from patients with chronic myeloid leukaemia) when these cells wer e cultured on preformed feeder layers established from normal marrow, CD44 appears to be part of a mechanism by which stromal elements can r egulate primitive normal haemopoietic cells but not their leukaemic (P h+) counterparts.