Signals mediated by FcγRIIA suppress the growth of B-lineage acute lymphoblastic leukemia cells

We examined Fc receptor expression and function in normal and leukemic human immature B cells. Fc receptor expression increased with normal B cell maturation: CD32⁺ cells composed 8.1% ± 1.2% (mean ± s.d.) of the least mature (CD34⁺ CD10⁺), 19.2% ± 5.7% of intermediate (CD34^-CD10⁺), and 82.4% ± 5.0% of mature (CD34^-CD10^-) bone marrow CD19⁺ B cells. Forty-five of 57 primary B-lineage acute lymphoblastic leukemia samples and all six cell lines studied expressed Fc receptors. By RT-PCR and antibody staining, FcγRIIA was the Fc receptor predominantly expressed in these cells. FcγRIIA ligation in RS4;11 and 380 cells induced tyrosine phosphorylation of CD32, CD19, CBL, SYK, P13-K p85 and SHIP, as well as RasGAP association with tyrosine-phosphorylated p62^dok. These signalling events resulted in a marked suppression of leukemia cell growth. After a 7-day exposure to anti-CD32, the recovery of ALL cells cocultured with stroma was reduced to 5.5% ± 2.8% of control values in 380 cells (n = 14), 19.4% ± 6.1% (n = 8) in RS4;11, and 4.0% ± 1.3% (n = 6) in KOPN 55bi. CD32 ligation also reduced cell recovery in five of seven CD32⁺ primary leukemia samples. Thus, FcγRIIA mediates signals that suppress the growth of lymphoid leukemia cells.