Signals mediated by FcgammaRIIA 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, FcgammaRIIA was the Fc receptor predominantly expressed in these cells. FcgammaRIIA 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 KOPN55bi. CD32 ligation also reduced cell recovery in five of seven CD32(+) primary leukemia samples. Thus, FcgammaRIIA mediates signals that suppress the growth of lymphoid leukemia cells.
Suzuki
T
T
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Coustan-Smith
E
E
Mihara
K
K
Campana
D
D
D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008024:Ligands; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction
D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D008024:Ligands; D017452:Receptors, IgG