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High intracellular content of cyclin‐dependent kinase inhibitor p27 Kip1 in early‐ and intermediate stage B‐cell chronic lymphocytic leukemia lymphocytes predicts rapid progression of the disease
Author(s) -
Wolowiec Dariusz,
Wojtowicz Marcin,
Ciszak Lidia,
Kosmaczewska Agata,
Frydecka Irena,
Potoczek Stanislaw,
UrbaniakKujda Donata,
KapelkoSlowik Katarzyna,
Kuliczkowski Kazimierz
Publication year - 2009
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2008.01196.x
Subject(s) - intracellular , chronic lymphocytic leukemia , cd38 , apoptosis , lymphocyte , flow cytometry , biology , leukemia , viability assay , immunology , cancer research , medicine , microbiology and biotechnology , biochemistry , cd34 , stem cell
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 p27 Kip1 . It has been suggested that its’ high expression may confer them survival advantage and lead to unfavorable prognosis, but the prognostic significance of p27 Kip1 expression for previously untreated, non‐advanced stage B‐CLL was not established. We studied a relationship between the intracellular level of p27 Kip1 of lymphocytes of early‐ and intermediate stage B‐CLL patients and their spontaneous apoptosis in vitro , as well as prognostic significance of p27 Kip1 in B‐CLL lymphocytes for the risk of disease progression. Intracellular p27 Kip1 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 p27 Kip1 expression was neither correlated with initial lymphocyte count, CD38 expression, cell viability nor spontaneous apoptosis ratio after 72‐h culture. Higher p27 Kip1 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 p27 Kip1 level in leukemic lymphocytes of early‐ and intermediate stage B‐CLL patients contributes to rapid progression of the disease.