Stellrecht C M, Mars W M, Miwa H, Beran M, Saunders G F
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Differentiation. 1991 Nov;48(2):127-35. doi: 10.1111/j.1432-0436.1991.tb00251.x.
Expression of the hematopoietic proteoglycan core protein (HpPG) gene was examined in normal peripheral blood, normal bone marrow, and leukemic peripheral blood leukocytes samples to assess the expression pattern of the HpPG gene in these cells and to ascertain points of regulation of this gene during hematopoiesis. In situ hybridization to normal bone marrow and peripheral blood leukocytes demonstrated that the gene was expressed in the promyelocytes at a approximately two fold greater level than in the segmented neutrophils and the expression decreased as the granulocytes matured. The ratio of expression in the other leukocytes to expression in the segmented neutrophils were as follows: eosinophils/basophils approximately 7; monocytes approximately 2; lymphocytes less than 1. Expression of the HpPG gene during myeloblast differentiation was assessed by Northern blot analysis of acute myelogenous leukemia (AML) RNA samples. The expression of this gene, when compared to the levels in HL-60 cells, was approximately ten fold lower in the poorly differentiated blast cells obtained from three AML patients classified M"0". Conversely, the expression in the more differentiated blast cells obtained from 10 of 11 AML patients classified as M1 and M2 were at levels similar to the levels in HL-60 cells. The expression level found in eight lymphoid leukemias was approximately ten fold or more lower than in HL-60 cells. Gene copy number determination confirmed that the HpPG gene is present in one copy per haploid genome. Thus the HpPG gene's expression pattern denotes a single copy gene being differentially expressed during hematopoiesis with initial regulation occurring very early in this developmental process and an additional up-regulatory event occurring during granule genesis.
为评估造血蛋白聚糖核心蛋白(HpPG)基因在正常外周血、正常骨髓及白血病外周血白细胞样本中的表达模式,并确定该基因在造血过程中的调控点,对其进行了检测。对正常骨髓和外周血白细胞进行原位杂交显示,该基因在前髓细胞中的表达水平比分叶核中性粒细胞高约两倍,且随着粒细胞成熟表达降低。其他白细胞与分叶核中性粒细胞的表达比例如下:嗜酸性粒细胞/嗜碱性粒细胞约为7;单核细胞约为2;淋巴细胞小于1。通过对急性髓性白血病(AML)RNA样本进行Northern印迹分析,评估了HpPG基因在成髓细胞分化过程中的表达。与HL-60细胞中的水平相比,从三名分类为M“0”的AML患者获得的低分化母细胞中该基因的表达约低10倍。相反,从11名分类为M1和M2的AML患者中的10名获得的分化程度更高的母细胞中的表达水平与HL-60细胞中的水平相似。在八种淋巴细胞白血病中发现的表达水平比HL-60细胞中的低约10倍或更多。基因拷贝数测定证实,HpPG基因在单倍体基因组中以单拷贝形式存在。因此,HpPG基因的表达模式表明,一个单拷贝基因在造血过程中差异表达,在这个发育过程的早期发生初始调控,在颗粒形成过程中发生额外的上调事件。