Experimental Oncology/Hematology, Bern University Hospital, Bern, Switzerland.
Leuk Res. 2010 Mar;34(3):393-8. doi: 10.1016/j.leukres.2009.08.037. Epub 2009 Sep 22.
Expression of N-myc downregulated gene 1 (NDRG1) is associated with growth arrest and differentiation of tumor cells. In hematopoietic cells, NDRG1 was identified in a screen for differentiation-related genes in human myelomonocytic leukemic U937 cells. In the present study, we found significantly higher NDRG1 mRNA levels in granulocytes of healthy donors than in primary acute myeloid leukemia (AML) cells. Another NDRG family member, NDRG2, was significantly higher expressed in normal macrophages compared to primary AML cells. Moreover, NDRG1 mRNA levels increased in two acute promyelocytic leukemia (APL) patients as well as in NB4 and HT93 APL cells upon all-trans retinoic acid (ATRA) therapy. In line with these observations, silencing of NDRG1 diminished neutrophil differentiation of leukemic cell lines. In conclusion, we found an association of low NDRG1 levels with an immature cell phenotype and provide evidence that NDRG1 is functionally involved in neutrophil maturation.
N-myc 下调基因 1（NDRG1）的表达与肿瘤细胞的生长抑制和分化有关。在造血细胞中，NDRG1 是在人髓单核白血病 U937 细胞的分化相关基因筛选中鉴定出来的。在本研究中，我们发现健康供体粒细胞中的 NDRG1 mRNA 水平明显高于原发性急性髓系白血病（AML）细胞。另一个 NDRG 家族成员 NDRG2 在正常巨噬细胞中的表达明显高于原发性 AML 细胞。此外，在全反式维甲酸（ATRA）治疗后，两名急性早幼粒细胞白血病（APL）患者以及 NB4 和 HT93 APL 细胞中的 NDRG1 mRNA 水平也升高。与这些观察结果一致，沉默 NDRG1 可减少白血病细胞系的中性粒细胞分化。总之，我们发现 NDRG1 水平低与不成熟细胞表型有关，并提供证据表明 NDRG1 参与中性粒细胞成熟的功能。
