Homeobox B genes expression in human leukemia cell lines during myelomonocytic differentiation

人白血病细胞系骨髓单核细胞分化过程中同源框 B 基因的表达

• 批准号: 07671190
• 负责人: OHNISHI Kazunori
• 金额: $ 1.41万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671190/
• 关键词: Homeobox Box gene; Acute myeloid leukemia; myeloid differentiation; Antisense nucleotide; アンチセンス核酸; 急性骨髄性白血病細胞株; ホメオボックス遺伝子; 骨髄性白血病

Homeobox genes (HOX) may have a regulatory function in the differentiation process of hematopoiesis. We examined the change of HOX B6 and HOX B9 mRNA expressions during the in vitro differentiation of four myeloid leukemia cell lines because HOX B6 may be involved closely in myeloid differentiation. NKM-1, HL-60, NB4, and NOMO-1 were established from acute leudemia of M2, M2, M3, and M5 subtype of the French-American-British classification, respectively. All-trans retinoic acid (ATRA), TPA,and G-CSF were used as differentiation inducers. Each cell line was wltured with each inducer and total RNA was isolated on day 1,2,3, or 5. HOX B mRNA was detected by Northem blotting and RT-PCR methods. HOX B6 and HOX B9 mRNAs were constitutively expressed in NKM-1, NB4, and NOMO-1, but were expressed at very low levels in HL-60, HOX B6 and HOX B9 mRNAs were also expressed in fresh acute myelocytic leukemia blasts. HOX B6 mRNA expression in HL-60, NKM-1, and NB4 cultured with ATRA increased on day … More 3 and decreased on day 5. HOX B6 mRNA expression in NKM-1 and NB4 cultured with TPA decreased on day 3. HOX B9 mRNA expression displayd changes similar to those of HOX B6 mRNA in NKM-1 and NB4. These results indicate that myeloid leukemia cell lines express HOX B6 and HOX B9, and that their respective mRNA expressions increase at an early stage of myeloid differentiation and then decrease during a late stage. HOX B6 mRNA expression decreased in NKM-1 which showed monocytoid differentiation by TPA induction. HOX B6 antisense-oligonucleotide inhibited the proliferation of NKM-1 and NB4, and it clearly did inhibit the proliferation of NKM-1, NB4, and HL-60 when stimulated with G-CSF.These results suggest that HOX B gene expression is related to simultaneous activation of cellular proliferation and differentiation, and that the aberrant expression may result in transcriptional regression of the genetic program of differentiation, and that HOX B gene expression plays a role in leukemogenesis. Less

同源盒型基因（HOX）在造血分化过程中可能具有调控作用。我们检测了四种髓系白血病细胞系体外分化过程中HOX B6和HOX B9 mRNA表达的变化，因为HOX B6可能密切参与髓系分化。NKM-1、HL-60、NB4、NOMO-1分别来源于法美英分型M2、M2、M3、M5亚型急性白血病。全反式维甲酸（ATRA）、TPA和G-CSF作为分化诱导剂。每个细胞系分别用每种诱导剂培养，并在第1、2、3、5天分离总RNA。采用Northem blotting和RT-PCR方法检测HOX B mRNA。HOX B6和HOX B9 mrna在NKM-1、NB4和NOMO-1中组成性表达，但在HL-60中表达极低水平，HOX B6和HOX B9 mrna也在新鲜急性髓细胞白血病母细胞中表达。经ATRA培养的HL-60、NKM-1和NB4中HOX B6 mRNA的表达在第3天升高，第5天降低。TPA培养NKM-1和NB4的HOX B6 mRNA表达在第3天降低。在NKM-1和NB4中，HOX B9 mRNA的表达变化与HOX B6相似。这些结果表明，髓系白血病细胞系表达HOX B6和HOX B9，并且它们各自的mRNA表达在髓系分化早期升高，在分化后期降低。在TPA诱导下，NKM-1呈单核细胞分化，HOX - B6 mRNA表达降低。HOX B6反意义寡核苷酸抑制NKM-1和NB4的增殖，并在G-CSF刺激下明显抑制NKM-1、NB4和HL-60的增殖。这些结果提示，HOX B基因的表达与细胞增殖和分化的同时激活有关，其表达异常可能导致分化遗传程序的转录倒退，HOX B基因的表达在白血病发生中起作用。少