Nuclear alterations during lymphocyte transformation: relationship to the heterogeneous morphologic presentations of...

A current hypothesis related to non-Hodgkin's lymphoma states that the wide variety of cytologic types in this disorder reflects morphologic alterations during different stages (G1, S, and G2) of the cell cycle involved in the blastogenic transformation of normal lymphocytes. In our investigations of biochemical and structural changes during lymphocyte transformation, we have used correlated stereologic morphometric analysis, assessment of chromatin organization, and autoradiography of human peripheral T-lymphocytes labeled with 3H-thymidine and stimulated with concanavalin A. These studies have confirmed that the characteristic increase in nuclear size and disaggregation of condensed chromatin masses precedes and is independent of DNA synthesis. Since the full range of morphologic alterations observed in lymphocyte transformation can occur in the G1 phase of this process, modifications to the above hypothesis are required. Assessment of the nuclear contour index following mitogen stimulation indicates that at least in this in vivo system, there is no cleaved or convoluted phase during the transformation of human peripheral T lymphocytes.