HOMEOBOX GENE EXPRESSION DURING HEMATOPOIESIS

同源框基因是一个编码转录因子的基因家族 被认为在胚胎发育过程中确定细胞命运的。我们和其他人有 几种同源异型盒基因在造血细胞中的表达 并提出同源异型盒基因在 造血术。具体地说，我最近展示了HOX C6和HLX 红系和髓系祖细胞的形成需要基因 体外克隆。 这项研究计划的主题是两个同源框基因，HLX和DLX- L。HLX是一种基因，我已经证明了它是形成 骨髓祖细胞集落。我提议做进一步的实验来阐明 该基因在骨髓生成中的功能及其功能的阐明 HLX蛋白的结构域。 DLX-L是我最近发现表达的一种新的同源异型盒基因 在T细胞和髓细胞中。对于这个基因，我建议克隆 全长c DNA，确定m RNA的大小，并确定是否存在反义 针对DLX-L的寡核苷酸可以抑制DLX-DLX的形成 造血祖细胞集落。 此外，我将探索同源异型盒基因可能 通过确定HLX和DLX-L基因是否参与白血病的发生 在白血病中的表达或基因结构发生了变化 是否可以检测到任何同源框基因的异位表达 白血病细胞。 预计这些研究将提供更好的了解 HLX和DLX-L在造血中的作用。

Homeobox genes are a family of genes coding for transcription factors thought to specify cell fate during embryogenesis. We and others have identified the expression of several homeobox genes in hematopoietic cells and have proposed that homeobox genes play a similar role in hematopoiesis. Specifically, I have recently shown that Hox C6 and HLX genes are required for the formation of erythroid and myeloid progenitor colonies in vitro. The subject of this research proposal are two homeobox genes, HLX and DLX- l. HLX is a gene which I have shown to be required for the formation of myeloid progenitor colonies. I propose further experiments to elucidate the function of this gene in myelopoiesis and to elucidate the functional domains of the HLX protein. DLX-l is a new homeobox gene, which I have recently found to be expressed in T cells and myeloid cells. For this gene, I propose to clone the entire cDNA, determine the mRNA size, and determine whether an antisense oligonucleotide directed against DLX-l can suppress the formation of hematopoietic progenitor colonies. In addition, I will explore the possibility that homeobox genes may participate in leukemogenesis, by determining whether HLX and DLX-l genes are altered either in expression or in gene structure in leukemias and whether ectopic expression of any homeobox genes can be detected in leukemia cells. These studies are expected to provide a better understanding of the function of HLX and DLX-l in hematopoiesis.