The effects of benzene and other leukaemogenic agents on haematopoietic stem and progenitor cell differentiation.

A characteristic shared by a diverse group of myelotoxic compounds and leukaemogens is the ability to act synergistically with granulocyte-macrophage colony stimulating factor (GM-CSF) in increasing clonogenic response. Pretreatment of murine or human bone marrow cells with the benzene metabolite, hydroquinone, but not phenol, catechol or trans, trans-muconaldehyde, results in a selective enhancement of GM-CSF but not an interleukin-3 (IL-3)-mediated clonogenic response. Clonal enhancement is preserved and magnified in enriched populations of CD34+ cells (> 95% purity), suggesting an intrinsic effect on haematopoietic progenitor cell (HPC) recruitment rather than a secondary effect involving accessory cytokines. Clonogenic enhancement of murine HPCs is not accompanied by alterations in GM-CSF receptor expression or ligand affinity and appears to be mediated via a p53-independent mechanism. These observations suggest that hydroquinone treatment alters recruitment and differentiation in a primitive subpopulation of CD34+ cells and are consistent with a role for altered stem cell differentiation in the development of chemically induced myelodysplasias.