Analysis of cell cycle characteristics and course of the disease in ANLL

Raza, Azra; Maheshwari, Yogesh; Brereton, William; Preisler, Harvey D.

doi:10.1002/ajh.2830240109

Cited by 15 publications

(1 citation statement)

References 16 publications

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“…In order to clarify the relation between Ag-NOR and the proliferative characteristics of leukemic cells, we stud ied the correlation in bone marrow leukemic cells between the number of Ag-NORs and the proportion in S-phase which is one of the most reliable indicators of cellular pro liferation and is related to the effect of therapy and prog nosis as well [22,23], To determine the in vivo S-phase size of leukemic cells, we have been using BrdU and its MoAb and staining by an immunohistochemical method which, in contrast to flow cytometry, made it possible to analyze cell kinetics in leukemias containing leukemic cells in low percentage.…”

Section: Discussionmentioning

confidence: 99%

Argyrophilic Proteins of the Nucleolar Organizer Region in Acute Leukemias and Its Relation to the S-Phase Fraction of Leukemic Cells

et al. 1992

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Nucleolar organizer regions (NORs) are loops of DNA which transcribes to ri-bosomal RNA. The NOR-related protein becomes visible in nucleus by a silver-staining technique under a light microscope, and it has been named argyrophilic protein of NOR (Ag-NOR). In various malignancies, the correlation between the proliferation potential of tumor cells or histological grade and the number of Ag-NORs has been reported. In this study, we investigated the Ag-NOR of acute leukemic cells and its relation to the in vivo proportion of bone marrow leukemic cells in DNA synthetic phase. The number of Ag-NORs in bone marrow leukemic cells was more than that in peripheral blood (means values 2.78 and 2.48, respectively, p < 0.01). This result shows that the number of Ag-NORs reflects the vigorous proliferative potential of bone marrow leukemic cells. However, no significant correlation was obtained between the number of Ag-NORs and the bromodeoxyuridine-labeling indices (r =0.2064). These results suggest that Ag-NOR might be one of the markers for cellular proliferation in leukemia, while DNA synthesis of leukemic cells do not seem to be directly related to Ag-NOR. In order to clarify the role of Ag-NOR in leukemia, further studies are needed.

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Section: Discussionmentioning

confidence: 99%

Argyrophilic Proteins of the Nucleolar Organizer Region in Acute Leukemias and Its Relation to the S-Phase Fraction of Leukemic Cells

et al. 1992

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Novel derivation of total cell cycle time in malignant cells using two DNA‐specific labels

Bokhari

Raza

1992

Cytometry

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Cell cycle kinetic analysis in vitro has conventionally been accomplished by labeling S-phase cells using two DNA specific labels given sequentially and separated from each other by a certain time interval. By counting the cells labeled by both versus those labeled by either one of the two labels, and using the formulas described by Wimber and Quastler, approximate values for durations of S-phase (Ts) and the total cell cycle (Tc) can be determined. More recently, instead of radioisotope labeled thymidine, two thymidine analogues have been used to label Sphase cells in vivo in a variety of human tumors based on the same principles. In the present report, new formulas are proposed for the calculation of Ts and Tc which are simpler to apply since only one type of labeled cells (those exiting Sphase as identified by containing only the first label) need to be differentiated from the remaining population for Tc calculations.Key terms: Thymidine analogues, cell cycle formulas, set theoryTo determine the rate of proliferation of cells by labeling S-phase cells sequentially with two varieties of radio-labeled thymidine, Wimber and Quastler (12) introduced their now classic equation, which has been extensively applied in cell cycle kinetic studies for approximately 30 years (5,11,14). We have also exploited this approach in studying large number of patients with acute myelocytic leukemia (AML). Our strategy required infusion of the first DNA-specific label bromodeoxyuridine (BrdUrd), in vivo and the second, tritiated thymidine label in vitro. By counting the number of leukemia cells which were singly labeled by either of the labels or doubly labeled, and employing the formulae described by Wimber and Quastler, we have been able to estimate the labeling index (LI), the duration of S-phase (Ts) and the total cell cycle time (Tc) of myeloblasts (8). Furthermore, we have determined the clinical relevance of these measurements by demonstrating a direct relationship between cell cycle times and duration of complete remission (7,9). With the rapid evolution of new techniques, better and more reliable probes are now available for detailed investigation of cell cycle kinetics. For example, instead of using the thymidine analogue bromodeoxyuridine in vivo and tritiated thymidine in vitro, we now routinely use iodo-deoxyuridine (IdUrd) and BrdUrd, both of which can be given in vivo. The actual counting of cells labeled by either one or both labels is an extremely tedious job, and because of the immunohistochemical techniques employed, it is not always possible to distinguish between a cell which contains BrdUrd alone or both BrdUrd and IdUrd. This problem is irrelevant in terms of results obtained since only IdUrd labeled cells need to be distinguished from all other labeled cells for the appropriate Ts calculations. However, attempts to improve upon the formula which would simplify the counting process lead us to the development of a reliable new mathematical equation which is being presented in this paper. This new equation can...

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Bone marrow cells in the DNA-synthesis-phase in the myelodysplastic syndrome and lymphome

Wenthzel¹,

Porwit²,

Lindahl³

et al. 1992

Med Oncol. & Tumor Pharmacother.

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Analysis of cell cycle characteristics and course of the disease in ANLL

Cited by 15 publications

References 16 publications

Argyrophilic Proteins of the Nucleolar Organizer Region in Acute Leukemias and Its Relation to the S-Phase Fraction of Leukemic Cells

Argyrophilic Proteins of the Nucleolar Organizer Region in Acute Leukemias and Its Relation to the S-Phase Fraction of Leukemic Cells

Novel derivation of total cell cycle time in malignant cells using two DNA‐specific labels

Bone marrow cells in the DNA-synthesis-phase in the myelodysplastic syndrome and lymphome

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