Insensitivity of chronic myeloid leukemia cells to inhibition of growth by prostaglandin E1.

The influence of E prostaglandins on the in vitro growth of chronic myeloid leukemia (CML)-committed granulopoietic precursors [colony-forming unit-culture (CFU-C)] has been investigated in a double-layer agar system in which CFU-C growth was stimulated by adherent monocytes. Addition of the prostaglandin synthesis inhibitor indomethacin to the feeder layer significantly increased the number of normal CFU-C, whereas CML CFU-C were unaffected. Exogenous prostaglandin E1 inhibited CML CFU-C growth at concentrations 1000-fold higher than those necessary to produce a similar effect on normal CFU-C. These data point to a lower than normal sensitivity of CML-committed granulopoietic precursors. It is suggested that derangement of the responsiveness of CML cells to prostaglandin regulation may play a role in the pathogenesis of uncontrolled leukemic proliferation.