ckshs expression is linked to cell proliferation in normal and malignant human lymphoid cells

Cyclin kinase sub-units (CKS) are known to interact with cyclin dependent k inases (CDKs), but their functions are not completely understood and their expression in human tissues is not documented. For analyzing relationships of CKS with cell proliferation and/or with differentiation, we investigated the expression of ckshs I and ckrhs2 in normal and malignant human lymphoi d cells. ckshs I and ckrhs2 expression appeared to be related to cell proli feration: (i) mRNAs increased with stimulation of normal peripheral-blood l ymphocytes, and from the G(1) to the SG(2)M phase in elutriated cells; (ii) P9 proteins were also induced by lymphocyte stimulation and were localized in nucleus where phosphorylated forms of CDK1 were also found; (iii) in vi tro, the phosphorylated forms of CDK1 and CDK2 were preferentially linked t o CKS. Among 45 patients presenting acute or chronic lymphoid malignancy, c kshs I and ckshs2 mRNAs varied in a similar way and were significantly corr elated to cell proliferation (p < 0.0001). When analysis was restricted sol ely to acute lymphoblastic leukemia (ALL) this correlation was still found and ckshs1 and ckshs2 were significantly more expressed in T-cell ALL than in B-cell-lineage ALL. These results confirm relationships between ckshs ex pression and cell proliferation, and pose the question of a link with cell differentiation. (C) 1999 Wiley-Liss, Inc.