PROGNOSTIC-SIGNIFICANCE OF THE CELL-CYCLE INHIBITOR P27(KIP1) IN CHRONIC B-CELL LYMPHOCYTIC-LEUKEMIA

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the ac cumulation of resting lymphocytes. The identification of p27(kip1), a cyclin-dependent kinase inhibitor that contributes to cell cycle arres t and represents a link between extracellular signals and cell cycle, prompted us to study p27 protein in the lymphocytes from 88 patients w ith B-CLL and 32 patients with other chronic B-lymphoproliferative dis orders. The expression of p27 protein was higher in B-CLL samples with variations among them. In B-CLL, p27 levels were independent of absol ute number of circulating lymphocytes, but strongly correlated with bo th lymphocyte and total tumor mass (TTM) doubling time. High p27 expre ssion was associated with a poorer overall prognosis. In vitro, there was an increased spontaneous survival of B-CLL cells expressing high p 27 levels. Interleukin 4 (IL-4) upregulated p27 levels in B-CLL cells, while fludarabine decreased p27 levels. Thus, our results indicate th at p27 may be a valuable kinetic marker in B CLL by providing Instanta neous estimation of the disease doubling time. In addition, these resu lts suggest that there is a link between p27 expression and the abilit y of CLL cells to undergo apoptosis. (C) 1998 by The American Society of Hematology.