PROLACTIN INCREASES THE SUSCEPTIBILITY OF PRIMARY LEUKEMIA-CELLS TO NK AND LAK EFFECTORS

Our previous studies have shown that prolactin (PRL), a pituitary and lymphocyte hormone and a ligand of the cytokine/hemopoietin receptors (R) superfamily, acts synergistically with interleukin (IL)-2 on the d evelopment of lymphokine activated killer (LAK) cells and enhances the effects of GM-CSF and IL-3 on myeloid progenitors' proliferation and differentiation. More recently, we have demonstrated that GM-CSF and I L-3 increase the sensitivity of acute myeloid leukemic (AML) cells to LAK activity. Together, these findings have prompted us to study the r ole of PRL on the target arm of the LAK response. We show here that CD 33+ blasts from AML patients express membrane PRL-R and that the PRL/P RL-R interaction is followed by increased susceptibility to natural ki ller (NK) (p < 0.02) and LAK (p < 0.001) cells. As predicted from the dimerization model of PRL-R and in agreement with previous reports, th e response of AML blasts to PRL was bell-shaped with a trend peak at 2 5 ng/ml. Although enhanced lysis occurred at the target recognition le vel, it was not accompanied by changes in the MHC class I, cellular ad hesion molecules, or myeloid differentiation antigens. Cell cycle recr uitment and lysis increased concurrently in three cases studied, sugge sting a modulatory action of PRL on the expression of putative cycle-r elated NK/LAK-target structures. Together, these data strengthen the r ole of PRL in the LAK response. Copyright (C) 1996 Elsevier Science Lt d.