Cell interactions and gene expression in early hematopoiesis.

As part of an investigation of the mechanisms controlling gene expression during lineage commitment, we have investigated the transcriptional status of hematopoietic lineage-specific genes and the interactions of early hematopoietic progenitor cells with stromal cells of the marrow microenvironment. The results indicate that a subset of otherwise lineage-restricted genes are transcriptionally active and/or DNAse I hypersensitive (i.e., "primed" for transcription) in multipotent, interleukin 3-dependent hematopoietic cells, and that they may become inaccessible and transcriptionally silent when cells are induced to adopt a single lineage during commitment. The external influences regulating gene expression in hematopoietic cells include binding interactions with stromal cells and exposure to locally presented growth factors. These interactions are thought to be essential for hematopoietic cell development and may be dysregulated in chronic myeloid leukemia.