正常供体和白血病患者白细胞中O-聚糖的生物合成：白血病细胞中O-聚糖核心2 UDP-葡萄糖胺：半乳糖β3 N-乙酰半乳糖胺α-R（从葡萄糖胺到N-乙酰半乳糖胺）β(1-6)-N-乙酰葡糖胺基转移酶增加。

Biosynthesis of O-glycans in leukocytes from normal donors and from patients with leukemia: increase in O-glycan core 2 UDP-GlcNAc:Gal beta 3 GalNAc alpha-R (GlcNAc to GalNAc) beta(1-6)-N-acetylglucosaminyltransferase in leukemic cells.

作者信息

Brockhausen I, Kuhns W, Schachter H, Matta K L, Sutherland D R, Baker M A

机构信息

Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.

出版信息

Cancer Res. 1991 Feb 15;51(4):1257-63.

PMID:1997166

Abstract

We have studied the biosynthesis of altered O-glycan structures on leukocytes from patients with chronic myelogenous leukemia and with acute myeloblastic leukemia (AML). It has been shown previously that the activity of CMP-NeuAc:Gal beta 1-3GalNAc alpha-R (sialic acid to galactose) alpha(2-3)-sialytransferase (EC 2.4.99.4) is increased in leukocytes from patients with chronic myelogenous leukemia (M. A. Baker, A. Kanani, I. Brockhausen, H. Schachter, A. Hindenburg, and R. N. Taub, Cancer Res., 47: 2763-2766, 1987) and with AML (A. Kanani, D. R. Sutherland, E. Fibach, K. L. Matta, A. Hindenburg, I. Brockhausen, W. Kuhns, R. N. Taub, D. van den Eijnden and M. A. Baker, Cancer Res., 50: 5003-5007, 1990). This increased activity may in part be responsible for the hypersialylation observed in leukemic leukocytes; however, hypersialylation may also be due to changes in underlying O-glycan structures. To test this hypothesis, we have assayed in normal human granulocytes and leukemic leukocytes several glycosyltransferases involved in the synthesis and elongation of the four common O-glycan cores. UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta(1-6)-GlcNAc transferase (EC 2.4.1.102), which synthesizes O-glycan core 2 (GlcNAc beta 1-6[Gal beta 1-3]GalNAc alpha), is significantly elevated in chronic myelogenous leukemia (4-fold) and AML (18-fold) leukocytes relative to normal human granulocytes. Neither normal nor leukemic cells show detectable activities of GlcNAc transferases which synthesize O-glycan core 3 (GlcNAc beta 1-3GalNAc-R) and core 4 (GlcNAc beta 1-6[GlcNAc beta 1-3] GalNAc-R) or the blood group I structure. The beta 3-GlcNAc transferase which elongates core 1 and core 2 was found at low levels in normal granulocytes but was not detectable in leukemic cells. The beta 3-GlcNAc transferase and beta 4-Gal transferase involved in poly-N-acetyllactosamine synthesis, as well as the beta 3-Gal transferase synthesizing core 1 (Gal beta 3 GalNAc), were present in all samples but were significantly increased in patients with AML. The observed changes are consistent with hypersialylation in leukemia.

摘要

我们研究了慢性粒细胞白血病患者和急性髓细胞白血病（AML）患者白细胞上改变的O-聚糖结构的生物合成。先前已表明，CMP-神经氨酸：Galβ1-3GalNAcα-R（唾液酸到半乳糖）α(2-3)-唾液酸转移酶（EC 2.4.99.4）的活性在慢性粒细胞白血病患者（M. A. 贝克、A. 卡纳尼、I. 布罗克豪森、H. 沙赫特、A. 欣登堡和R. N. 陶布，《癌症研究》，47: 2763 - 2766, 1987）和AML患者（A. 卡纳尼、D. R. 萨瑟兰、E. 菲巴赫、K. L. 马塔、A. 欣登堡、I. 布罗克豪森、W. 库恩斯、R. N. 陶布、D. 范登艾恩德和M. A. 贝克，《癌症研究》，50: 5003 - 5007, 1990）的白细胞中增加。这种增加的活性可能部分是白血病白细胞中观察到的高唾液酸化的原因；然而，高唾液酸化也可能是由于潜在O-聚糖结构的变化。为了验证这一假设，我们在正常人粒细胞和白血病白细胞中检测了几种参与四种常见O-聚糖核心合成和延长的糖基转移酶。UDP-GlcNAc：Galβ1-3GalNAc-R（GlcNAc到GalNAc）β(1-6)-GlcNAc转移酶（EC 2.4.1.102），其合成O-聚糖核心2（GlcNAcβ1-6[Galβ1-3]GalNAcα），在慢性粒细胞白血病（4倍）和AML（18倍）白细胞中相对于正常人粒细胞显著升高。正常细胞和白血病细胞均未显示出合成O-聚糖核心3（GlcNAcβ1-3GalNAc-R）和核心4（GlcNAcβ1-6[GlcNAcβ1-3]GalNAc-R）或血型I结构的GlcNAc转移酶的可检测活性。延长核心1和核心2的β3-GlcNAc转移酶在正常粒细胞中含量较低，但在白血病细胞中未检测到。参与多聚N-乙酰乳糖胺合成的β3-GlcNAc转移酶和β4-Gal转移酶，以及合成核心1（Galβ3GalNAc）的β3-Gal转移酶，在所有样本中均存在，但在AML患者中显著增加。观察到的变化与白血病中的高唾液酸化一致。