Complexity of the immediate early response of myeloid cells to terminal differentiation and growth arrest includes ICAM-1, Jun-B and histone variants.

Differentiation inducible leukemic as well as normal myeloid precursors treated with physiological myeloid differentiation inducer have been used to explore the immediate early genetic response of cells to terminal differentiation and growth arrest stimuli. cDNA clones of 12 distinct genes, referred to as MyD genes, which are activated in the absence of protein synthesis following induction of myeloid differentiation and growth arrest have been isolated. Sequence analysis of both ends of MyD cDNA clones, and analysis of MyD gene expression following induced differentiation of M1D+ and normal myeloid precursors, has shown that the immediate early genetic response of myeloid cells to the induction of terminal differentiation is complex. This complex response involves a variety of genes, some of which are known and others unknown, including: transient induction of ICAM-1, a gene encoding for a ligand to a cell surface adhesion receptor; stable induction of Jun-B, a gene encoding for a nuclear transcription factor; and increased expression of histone genes which encode for terminal differentiation histone variants. These findings demonstrate that terminal differentiation and growth arrest immediate early response genes encode for at least three distinct types of gene products, which may play a role to reprogram the transcriptional activity of proliferating and non-differentiated cells towards their conversion into terminally differentiated nonproliferating cells.