HOMEOBOX GENE EXPRESSION DURING HEMATOPOIESIS

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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.