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白血病成髓细胞与针对唾液酸化-Le(x)及其他乳糖系列2型链抗原的单克隆抗体的反应性谱:与正常造血祖细胞无反应性

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.

作者信息

Muroi K, Suda T, Nojiri H, Ema H, Amemiya Y, Miura Y, Nakauchi H, Singhal A, Hakomori S

机构信息

Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.

出版信息

Blood. 1992 Feb 1;79(3):713-9.

PMID:1370643
Abstract

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.

摘要

我们研究了造血细胞及其祖细胞中乳糖系列2型抗原的表达谱,并与白血病白细胞进行了比较。各种抗2型链单克隆抗体(MoAbs)与12例急性髓细胞性白血病(AML)患者及2例急性未分类白血病(AUL)患者的白血病原始细胞的反应谱显示,抗唾液酸化-Le(x) MoAb SNH3与所有患者(14例中的14例)超过95%的白血病原始白细胞群体强烈反应。另一种抗唾液酸化-Le(x) MoAb FH6的反应性低于SNH3(14例患者中的12例),而抗-Le(y) MoAb AH6仅与14例患者中的8例有反应。另一方面,所有抗2型链MoAbs均未与从三名健康志愿者独立获取的CD34+正常成人骨髓(BM)单个核细胞发生反应。MoAb SNH3而非FH6或AH6,对这些患者的白血病原始细胞以及髓性白血病细胞系HL60表现出补体介导的细胞毒性。用SNH3和补体处理正常BM单个核细胞可不完全抑制粒细胞-巨噬细胞集落形成单位(CFU-GM),但不抑制红系爆式集落形成单位(BFU-E)。造血祖细胞以及体外造血集落(CFU-GM和BFU-E)中缺乏2型链抗原表达强烈提示,应用抗碳水化合物MoAbs,尤其是抗唾液酸化-Le(x),可能有助于清除浸润于BM中的白血病原始粒细胞、清除BM中的白血病原始细胞以及促进自体BM移植。

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