Reactivity profiles of leukemic myeloblasts with monoclonal antibodies directed to sialosyl-Le(x) and other lacto-series type 2 chain antigens:absence of reactivity with normal hematopoietic progenitor cells.
We investigated the expression profiles of lacto-series type 2 antigens in hematopoietic cells and their progenitors, in comparison with leukemic leukocytes. Reactivity profiles of various anti-type 2 chain monoclonal antibodies (MoAbs) with leukemic blasts from 12 patients with acute myeloblastic leukemia (AML) and those from two patients with acute unclassified leukemia (AUL) show that anti-sialosyl-Le(x) MoAb SNH3 reacted strongly with greater than 95% of leukemic blast leukocyte populations from all patients (14 of 14). Another anti-sialosyl-Le(x) MoAb, FH6, showed less reactivity than SNH3 (12 of 14 patients), while anti-Le(y) MoAb AH6 showed reactivity with only 8 of 14 patients. On the other hand, none of the anti-type 2 chain MoAbs reacted with CD34+ normal adult bone marrow (BM) mononuclear cells obtained independently from three healthy volunteers. MoAb SNH3, but not FH6 or AH6, showed complement-mediated cytotoxicity to leukemic blasts from these patients, as well as to myelogenous leukemia cell line HL60. Colony-forming unit granulocyte-macrophage (CFU-GM), but not burst-forming unit-erythroid (BFU-E), was incompletely inhibited by treatment of normal BM mononuclear cells with SNH3 and complement. The absence of type 2 chain antigen expression in hematopoietic progenitor cells and in in vitro hematopoietic colonies (CFU-GM and BFU-E) strongly suggests that application of anti-carbohydrate MoAbs, particularly anti-sialosyl-Le(x) could be useful for elimination of leukemic myeloblasts infiltrating in BM, for purging of leukemic blasts in BM, and for facilitation of autologous BM transplantation.
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
K
K
Muroi
T
T
Suda
H
H
Nojiri
H
H
Ema
Y
Y
Amemiya
Y
Y
Miura
H
H
Nakauchi
A
A
Singhal
S
S
Hakomori
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D018952:Antigens, CD34; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D002240:Carbohydrate Sequence; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000276:immunology*; D007983:Lewis Blood Group Antigens / Q000737:chemistry / Q000276:immunology; D016256:Lewis X Antigen / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D012794:Sialic Acids / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D018952:Antigens, CD34; D015295:Antigens, Tumor-Associated, Carbohydrate; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D012794:Sialic Acids