High intracellular content of cyclin-dependent kinase inhibitor p27Kip1 in early- and intermediate stage B-cell chronic lymphocytic leukemia lymphocytes predicts rapid progression of the disease

• Published in: European journal of haematology Vol. 82; no. 4; pp. 260 - 266
• Main Authors: Wolowiec, Dariusz, Wojtowicz, Marcin, Ciszak, Lidia, Kosmaczewska, Agata, Frydecka, Irena, Potoczek, Stanislaw, Urbaniak-Kujda, Donata, Kapelko-Slowik, Katarzyna, Kuliczkowski, Kazimierz
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2009
• Subjects: apoptosis; chronic lymphocytic leukemia; p27Kip1
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/j.1600-0609.2008.01196.x

Previous studies showed that peripheral blood lymphocytes of B‐cell chronic lymphocytic leukemia (B‐CLL) displayed a high intracellular level of cell cycle inhibitory protein p27Kip1. It has been suggested that its’ high expression may confer them survival advantage and lead to unfavorable prognosis, but the prognostic significance of p27Kip1 expression for previously untreated, non‐advanced stage B‐CLL was not established. We studied a relationship between the intracellular level of p27Kip1 of lymphocytes of early‐ and intermediate stage B‐CLL patients and their spontaneous apoptosis in vitro, as well as prognostic significance of p27Kip1 in B‐CLL lymphocytes for the risk of disease progression. Intracellular p27Kip1 content of peripheral blood lymphocytes obtained from 48 previously untreated 0–II Rai stage B‐CLL patients was determined by flow cytometry. The viability and apoptosis of those lymphocytes after 72‐h culture were also assessed. During the follow‐up period (6–71 months, median 59.5), we recorded the time elapsed to the doubling of lymphocyte count, progression to a higher Rai stage and the appearance of indications for cytostatic treatment. The p27Kip1 expression was neither correlated with initial lymphocyte count, CD38 expression, cell viability nor spontaneous apoptosis ratio after 72‐h culture. Higher p27Kip1 level was related to the probability of earlier occurrence of each of three above‐mentioned events. We did not find a prognostic significance of in vitro cell viability nor apoptosis as to the risk of disease progression. Our results indicate that elevated intracellular p27Kip1 level in leukemic lymphocytes of early‐ and intermediate stage B‐CLL patients contributes to rapid progression of the disease.