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Prognostic Significance of the Cell Cycle Inhibitor
p27Kip1 in Chronic B-Cell Lymphocytic Leukemia
Radovan Vrhovac,
Alain Delmer,
Ruoping Tang,
Jean-Pierre Marie,
Robert Zittoun, and
Florence Ajchenbaum-Cymbalista
From the Laboratoire de Cinétique et Culture Cellulaires,
Formation associée Claude Bernard, Service d'Hématologie,
Hôpital Hôtel-Dieu, Assistance Publique, Hôpitaux de
Paris (AP-HP), Paris, France.
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the
accumulation of resting lymphocytes. The identification of
p27kip1, a cyclin-dependent kinase inhibitor that
contributes to cell cycle arrest and represents a link between
extracellular signals and cell cycle, prompted us to study p27 protein
in the lymphocytes from 88 patients with B-CLL and 32 patients with
other chronic B-lymphoproliferative disorders. The expression of p27
protein was higher in B-CLL samples with variations among them. In
B-CLL, p27 levels were independent of absolute number of circulating lymphocytes, but strongly correlated with both lymphocyte and total
tumor mass (TTM) doubling time. High p27 expression was associated with
a poorer overall prognosis. In vitro, there was an increased
spontaneous survival of B-CLL cells expressing high p27 levels.
Interleukin-4 (IL-4) upregulated p27 levels in B-CLL cells, while
fludarabine decreased p27 levels. Thus, our results indicate that p27
may be a valuable kinetic marker in B-CLL by providing instantaneous
estimation of the disease doubling time. In addition, these results
suggest that there is a link between p27 expression and the ability of
CLL cells to undergo apoptosis.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4694-4700
© 1998 by The American Society of Hematology.
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