Expression of Inhibitors of Cyclin-Dependent Kinases in Leukemia

Overview

Background.
Leukemias develop due to defects in proliferation, differentiation and apoptosis, which take place instem cells or progenitors of hematopoiesis. These processes have several crossing points, one of them is the role ofinhibitors of cyclin-dependent kinases. The aim of this study was to study the expression of cyclin-dependent kinasesinhibitors p21 Cip and p27 Kip and expression of proliferative antigen Ki-67 in leukocytes of human leukemia.Methods and Results. The expression of cyclin-dependent kinases inhibitors was detected at mRNA level mainlyby comparative reverse-transcription polymerase chain reaction and in selected samples also by the real-timepolymerase chain reaction. While p27 Kip expression in leukocytes of leukemic patients and healthy persons wasuniversal, large differences in expression of p21 Cip were found both among individual patients of the same type ofleukemia and between different types of leukemias and healthy persons. The p21 Cip expression was significantlyhigher in acute leukemias than in chronic ones and healthy persons. A comparison of p21 Cip expression with theclinical outcome of the leukemic patients showed that the group of 14 acute leukemia patients surviving more than30 months had a significantly lower expression of p21 Cip than 12 patients of this type of leukemia who died withinthis time limit. Moreover, the results obtained on a smaller set of acute promyelocytic leukemia patients indicatedthat the lower p21 expression is connected with a better prognosis.Conclusion. Our results pointed out the importance of the cyclin-dependent kinase inhibitor p21 Cip in humanleukemias and indicated that the lower p21 Cip expression might be a positive prognostic factor in acute myeloidleukemia patients.

Key words:
leukemia, polymerase chain reaction, enzyme inhibitors, p21 Cip, prognosis.