Ultrastructural Cell Cycle-specific Nuclear and Nucleolar Changes of Human Leukemic Lymphoblasts1

To identify cell cycle-specific ultrastructural markers in acute lymphoblastic leukemia, we labeled bone marrow lymphoblasts with [3H]thymidine, separated them according to cell size by velocity sedimentation at 1 x g, and then identified the pattern of changes within the nucleus of the cells according to phase of the cell cycle. The smallest and most slowly sedimenting cells (probably in G,, phase) had prominent, condensed nuclear chromatin and adjacent small nucleoli with segregated substructure and a distinct focus of pars amorpha, which contained pyroantimonatereactive cation. Slightly larger cells (probably in G, phase) contained a more irregular nuclear profile; dispersed nu clear chromatin; and large, round, centrally located nu cleoli with increased granular component, dispersed foci of pars amorpha, dense fibrillar component, and decreased nucleolus-associated chromatin. During early S phase, [3H]thymidine diffusely labeled the nucleus; the nucleoli, usually within the nuclear periphery, had increased nucleo lus-associated chromatin. In late S-phase cells, [3H]thymidine