Circadian cell cycle variations of erythro- and myelopoiesis in humans

By use of a multiparameter flow cytometric method with specific surface markers, circadian (24-h) variations in cell cycle distribution have been studied in 19 healthy male volunteers by sampling bone marrow (BM) every 4-5 h during 24-h periods. Admixture of peripheral blood during the sampling was specifically adjusted for, and the fractions of cells in DNA synthetic phase were measured for different hemopoietic cell lineages. Significant circadian variations in DNA S-phase were demonstrated both in myelo- and erythropoiesis of the human BM, with 75% (myeloid) and 80% (erythroid) of the volunteers showing highest activity (values) of DNA S-phase during the day and lowest activity (values) between midnight and 04:00 h. A temporal relationship in the circadian variation of S-phase and G2/M-phase was demonstrated between the myeloid and erythroid cell lineages. The highest fractions of S-phase cells were found in erythropoiesis, while the highest circadian stage dependent variation was found in myelopoiesis. The existence of a similar phasing in DNA synthetic activity for myelopoietic and erythropoietic cells in the human bone marrow indicates that the circadian rhythmicity of hemopoiesis may be caused by a common regulatory mechanism. These findings may be relevant with regard to optimizing the use of cytotoxic drugs and hemopoietic growth factors by taking into consideration the intrinsic (endogenous) circadian variation in proliferative activity of human BM subpopulations.