Colony-forming unit-granulocyte-macrophage and DNA synthesis of human bone marrow are circadian stage-dependent and show covariation

Abstract Bone marrow samples from sternum and iliac crests were harvested every 4 hours during 19 24-hour periods from 16 healthy male volunteers, and myeloid progenitor cells were cultured by the colony-forming unit- granulocyte-macrophage (CFU-GM) assay. A large interindividual variation was observed in the mean number of colonies during each 24- hour period, with the highest 24-hour mean colony number being about 600% greater than the lowest (range: 16 +/- 2.3 to 100.3 +/- 4.5). For each individual the difference between the lowest and highest colony number throughout the day ranged from 47.4% to 256.3% of the mean colony number of each series. A circadian stage-dependent variation in the number of colony-forming units of myeloid progenitor cells (CFU-GM) of human bone marrow was demonstrated, with values 150% higher, on the average, during the day as compared with the night. The overall data (891 CFU-GM replicates) exhibited a significant 24-hour rhythm (P less than .001) with an acrophase at midday (12.09 hours with 95% confidence limits from 10.32 to 13.49 hours) and a trough at midnight. This 24- hour variation was found to covary with DNA synthesis in the total proliferating bone marrow cell population. A seasonal effect on CFU-GM numbers was detected by ANOVA (P = .014) and by the least squares fit of a 1-year cosine (P = .015), with the highest number found in summer. The potential relevance of these findings should be examined in relation to cytotoxic cancer therapy, use of hematopoietic growth factors, and bone marrow transplantation.

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Colony-forming unit-granulocyte-macrophage and DNA synthesis of human bone marrow are circadian stage-dependent and show covariation

Blood ◽

10.1182/blood.v79.9.2281.bloodjournal7992281 ◽

1992 ◽

Vol 79 (9) ◽

pp. 2281-2287 ◽

Cited By ~ 50

Author(s):

R Smaaland ◽

OD Laerum ◽

RB Sothern ◽

O Sletvold ◽

R Bjerknes ◽

...

Keyword(s):

Bone Marrow ◽

Dna Synthesis ◽

Progenitor Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Colony Forming Unit ◽

Myeloid Progenitor ◽

Myeloid Progenitor Cells ◽

Colony Number ◽

The Mean

Bone marrow samples from sternum and iliac crests were harvested every 4 hours during 19 24-hour periods from 16 healthy male volunteers, and myeloid progenitor cells were cultured by the colony-forming unit- granulocyte-macrophage (CFU-GM) assay. A large interindividual variation was observed in the mean number of colonies during each 24- hour period, with the highest 24-hour mean colony number being about 600% greater than the lowest (range: 16 +/- 2.3 to 100.3 +/- 4.5). For each individual the difference between the lowest and highest colony number throughout the day ranged from 47.4% to 256.3% of the mean colony number of each series. A circadian stage-dependent variation in the number of colony-forming units of myeloid progenitor cells (CFU-GM) of human bone marrow was demonstrated, with values 150% higher, on the average, during the day as compared with the night. The overall data (891 CFU-GM replicates) exhibited a significant 24-hour rhythm (P less than .001) with an acrophase at midday (12.09 hours with 95% confidence limits from 10.32 to 13.49 hours) and a trough at midnight. This 24- hour variation was found to covary with DNA synthesis in the total proliferating bone marrow cell population. A seasonal effect on CFU-GM numbers was detected by ANOVA (P = .014) and by the least squares fit of a 1-year cosine (P = .015), with the highest number found in summer. The potential relevance of these findings should be examined in relation to cytotoxic cancer therapy, use of hematopoietic growth factors, and bone marrow transplantation.

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The Effect of Anti-i on Early Myeloid Progenitor Cells in Human Bone Marrow

Experimental Hematology Today 1979 ◽

10.1007/978-1-4612-6179-7_8 ◽

1979 ◽

pp. 51-54

Author(s):

C. J. O’Hara ◽

K. H. Shumak ◽

G. B. Price

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Myeloid Progenitor ◽

Myeloid Progenitor Cells

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DNA synthesis in human bone marrow is circadian stage dependent

Blood ◽

10.1182/blood.v77.12.2603.bloodjournal77122603 ◽

1991 ◽

Vol 77 (12) ◽

pp. 2603-2611 ◽

Cited By ~ 1

Author(s):

R Smaaland ◽

OD Laerum ◽

K Lote ◽

O Sletvold ◽

RB Sothern ◽

...

Keyword(s):

Bone Marrow ◽

Dna Synthesis ◽

Sampling Procedure ◽

Mean Value ◽

Time Of Day ◽

Human Bone ◽

Human Bone Marrow ◽

Hematopoietic Growth Factors ◽

Proliferating Cells ◽

The Mean

Fraction of human bone marrow (BM) cells in DNA synthesis has been studied by sampling BM from the sternum or the iliac crests every 4 hours during one 24-hour period in 16 healthy male volunteers. Three of the subjects underwent the sampling procedure twice, resulting in 19 24- hour profiles. The percentage of cells in DNA synthesis measured by flow cytometry demonstrated a large variation along the circadian time scale for each 24-hour profile, with a range of variation from 29% to 339% from lowest to highest value. Seventeen profiles (89.5%) had the highest DNA synthesis during waking hours between 08:00 hours and 20:00 hours, and the lowest percentage of cells in DNA synthesis between 00:00 hours and 04:00 hours. The mean value of the lowest DNA synthesis for each 19 24-hour period was 8.7% +/- 0.6%, while the mean value of the highest DNA synthesis was 17.6% +/- 0.6%, ie, a twofold difference. There was no difference in DNA synthesis between winter and summer. A significantly higher DNA synthesis was demonstrated for samples obtained from sternum as compared with the iliac crests, but the same circadian pattern was demonstrated for both localizations. By taking circadian stage-dependent variations in DNA synthesis into account it may be possible to reduce BM sensitivity to cytotoxic chemotherapy, to increase the effect of hematopoietic growth factors as well as increase the fraction of proliferating cells with careful selection of time of day for harvesting BM cells for auto- or allografting.

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DNA synthesis in human bone marrow is circadian stage dependent

Blood ◽

10.1182/blood.v77.12.2603.2603 ◽

1991 ◽

Vol 77 (12) ◽

pp. 2603-2611 ◽

Cited By ~ 105

Author(s):

R Smaaland ◽

OD Laerum ◽

K Lote ◽

O Sletvold ◽

RB Sothern ◽

...

Keyword(s):

Bone Marrow ◽

Dna Synthesis ◽

Sampling Procedure ◽

Mean Value ◽

Time Of Day ◽

Human Bone ◽

Human Bone Marrow ◽

Hematopoietic Growth Factors ◽

Proliferating Cells ◽

The Mean

Abstract Fraction of human bone marrow (BM) cells in DNA synthesis has been studied by sampling BM from the sternum or the iliac crests every 4 hours during one 24-hour period in 16 healthy male volunteers. Three of the subjects underwent the sampling procedure twice, resulting in 19 24- hour profiles. The percentage of cells in DNA synthesis measured by flow cytometry demonstrated a large variation along the circadian time scale for each 24-hour profile, with a range of variation from 29% to 339% from lowest to highest value. Seventeen profiles (89.5%) had the highest DNA synthesis during waking hours between 08:00 hours and 20:00 hours, and the lowest percentage of cells in DNA synthesis between 00:00 hours and 04:00 hours. The mean value of the lowest DNA synthesis for each 19 24-hour period was 8.7% +/- 0.6%, while the mean value of the highest DNA synthesis was 17.6% +/- 0.6%, ie, a twofold difference. There was no difference in DNA synthesis between winter and summer. A significantly higher DNA synthesis was demonstrated for samples obtained from sternum as compared with the iliac crests, but the same circadian pattern was demonstrated for both localizations. By taking circadian stage-dependent variations in DNA synthesis into account it may be possible to reduce BM sensitivity to cytotoxic chemotherapy, to increase the effect of hematopoietic growth factors as well as increase the fraction of proliferating cells with careful selection of time of day for harvesting BM cells for auto- or allografting.

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