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Changes Observed in the Growth Fraction, Labeling Index, Duration of S Phase, and Total Cell Cycle Times of HL-60 Cells as They Undergo Differentiation in Response to Retinoic Acid¹

Department of Hematologic Oncology, Roswell Park Memorial Institute, Buffalo, New York 14263 [S. G., Z. Y., S. I., A. R.]; Department of Microbiology and Immunology, Lucille Markey Cancer Center, University of Kentucky Medical Center, Lexington, Kentucky 40536 [J. F.]; and Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030 [A. B.]

To assess the changes in the proliferative characteristics that occur during maturation, HL-60 cells were induced to differentiate along the granulocytic pathway by retinoic acid. Differentiation was documented by morphology, functional markers, and cytochemical staining. Durations of S phase, total cell cycle time, and the percentage of S-phase cells were determined simultaneously at each time point. In addition, the expression of two cell cycle related proteins with molecular weights of 110,000 (p110 measured by monoclonal antibody 5C2) and 145,000 (measured by monoclonal antibody p145) were measured to estimate the number of cycling cells or the "growth fraction."

Our data demonstrate that as HL-60 cells undergo maturation in response to retinoic acid, a large proportion of cells exit from the cycle, the majority lose their proliferative potential, and the total cell cycle time becomes markedly longer. The slowing of the cell cycle seems to be the result of a prolongation in both S phase and the G₁ phase of the cycle. We conclude that more mature myeloid cells cycle more slowly than immature cells. The clinical implications of these findings in myeloid leukemias are discussed.

¹ This work was supported by National Cancer Institute Grants CA28734-05 and CA41285-03.

² To whom requests for reprints should be addressed, at Department of Hematologic Oncology, Roswell Park Memorial Institute, 666 Elm St., Buffalo, NY 14263.

Received 4/ 1/88. Revised 7/11/88. Accepted 7/29/88.