EXPRESSION OF CELL-CYCLE REGULATORY PROTEINS IN CHRONIC LYMPHOCYTIC LEUKEMIAS - COMPARISON WITH NON-HODGKINS-LYMPHOMAS AND NONNEOPLASTIC LYMPHOID-TISSUE

The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peri pheral blood lymphocytes (PBL) from 25 cases of chronic lymphocytic le ukemias (CLL) in order to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison, we also studied the expression of th ese proteins in: 23 samples of non-Hodgkin's lymphoma (NHL) tissue of different histological types, 10 samples of non-neoplastic lymphoid ti ssue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated PBL (PHA-PB L) from three healthy donors. Samples were lysed and proteins were res olved on polyacrylamide gel followed by Western blot. The expression o f cdk4 and cyclin E, both known to act in early cell cycle stage, was approximately on the same level in all groups of lymphoid pathology ex amined. in particular, we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk4 positive, ie they expresse d these markers over twice the level of non-stimulated healthy PBL. Th e cdk1 expression was above the level seen in NS-PBL in 14 (56%) cases , but the average expression was significantly lower than in the other tissues examined, including low-grade lymphomas. Cdk2 expression was comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL and in NLT. Cyclins A and B, normally observed in advanced c ell cycle phases, were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some cases, indicate that the CLL cells ar e not quiescent, but are blocked in an early stage of the G(1) cell cy cle phase, and/or that the expression of these proteins is pathologica lly deregulated.