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.
Muroi
K
K
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
Suda
T
T
Nojiri
H
H
Ema
H
H
Amemiya
Y
Y
Miura
Y
Y
Nakauchi
H
H
Singhal
A
A
Hakomori
S
S
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