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Cytophotometry of granulocytes in chronic granulocytic leukemia patients. Part I. Cell cycle distribution, S-phase
V M Kotelnikov1, N G Lishmanova, N D Khoroshko
1Central Institute of Haematology and Blood Transfusion, Moscow State University, USSR.
Insights
Chronic granulocytic leukemia (CGL) shows altered granulocyte cell cycle dynamics. During blast crisis, CGL cells exhibit significantly higher S+G2 phase percentages than normal or acute myeloblastic leukemia cells.
Area of Science:
- Hematology
- Cell Biology
- Cancer Research
Background:
- Chronic granulocytic leukemia (CGL) is characterized by abnormal proliferation of myeloid cells.
- Understanding the cell cycle kinetics of granulocytes in CGL is crucial for disease monitoring and treatment.
Purpose of the Study:
- To investigate the cell cycle distribution of granulocytes in chronic phase and blast crisis of CGL.
- To compare the S+G2 phase percentages in CGL with normal bone marrow and acute myeloblastic leukemia.
- To analyze DNA synthesis rates and morphometric/cytochemical characteristics of neutrophils in CGL.
Main Methods:
- Feulgen-DNA cytophotometry to determine cell cycle phases (G1, S, G2, M).
- 3H-thymidine incorporation to assess DNA synthesis.
- Quantitative cytochemistry (PAS, Sudan, myeloperoxidase activity) and morphometry of neutrophils.
Main Results:
- Granulocytes in chronic phase CGL had lower S+G2 proportions (18.7% marrow, 16.7% blood) compared to normal bone marrow (42.4%).
- Blast crisis CGL showed significantly higher S+G2 percentages (39.3% marrow, 38.7% blood) than acute myeloblastic leukemia (10.8% marrow, 5.1% blood).
- Thymidine labeling index underestimated S-phase cells, with DNA synthesis rate constant but uptake increasing late in S-phase; neutrophil characteristics were altered in chronic phase but normal in blast crisis.
Conclusions:
- CGL granulocytes exhibit distinct cell cycle alterations, with increased S+G2 phase during blast crisis.
- Mature neutrophils in blast crisis likely originate from normal granulocyte progenitors, suggesting differential regulation.
- Feulgen-DNA cytophotometry and thymidine incorporation provide complementary insights into CGL cell proliferation.
Abstract:
In the chronic phase of CGL the proportion of granulocytes in S + G2 was lower (18.7 +/- 1.3% in marrow and 16.7 +/- 2.4% in blood) than in normal bone marrow (42.4 +/- 2.9%) as studied by Feulgen-DNA cytophotometry. During the blast crisis the percentage of S + G2 blasts was 39.3 +/- 8.4 in marrow and 38.7 +/- 7.8 in blood which was much higher than in acute myeloblastic leukemia patients (10.8 +/- 1.4 and 5.1 +/- 1.0). Thymidine labelling index values were lower than the percentage of cytophotometrically detected S-phase cells: up to 28% of cells with Feulgen-DNA content corresponding to S-phase did not incorporate 3H-thymidine. The rate of DNA synthesis remained constant during the S-phase but 3H-thymidine uptake increases towards the end of the S-phase. Morphometric parameters and quantitative cytochemical (PAS, Sudan, myeloperoxidase activity) characteristics of polymorphonuclear neutrophils were altered during the chronic phase of the disease but remained in the normal range during the blast crisis. Mature neutrophils in the blast crisis are assumed to originate from normal granulocyte progenitors.