Diverse effects of anti‐CD44 antibodies on the stromal cell‐mediated support of normal but not leukaemic (CML) haemopoiesis in vitro

We have identified three non‐cross‐reacting anti‐human CD44 monoclonal antibodies that have significant positive or negative (or no) effects on normal human haemopoiesis in the long‐term culture (LTC) system. These 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 purified CD34+CD38− normal marrow cells were placed on pre‐established normal marrow feeder layers in the presence or absence of each antibody. The effects seen were rapid and sustained, and dependent on the presence of a preformed feeder layer. Interestingly, the same anti‐CD44 antibodies had no effect on the maintenance of leukaemic (Ph+) progenitors (from patients with chronic myeloid leukaemia) when these cells were cultured on preformed feeder layers established from normal marrow. CD44 appears to be part of a mechanism by which stromal elements can regulate primitive normal haemopoietic cells but not their leukaemic (Ph+) counterparts.