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

Abstract

Cyclin kinase sub-units (CKS) are known to interact with cyclin-dependent kinases (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 ckshs1 and ckshs2 in normal and malignant human lymphoid cells. ckshs1 and ckshs2 expression appeared to be related to cell proliferation: (i) mRNAs increased with stimulation of normal peripheral-blood lymphocytes, and from the G1 to the SG2M 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 vitro, the phosphorylated forms of CDK1 and CDK2 were preferentially linked to CKS. Among 45 patients presenting acute or chronic lymphoid malignancy, ckshs1 and ckshs2 mRNAs varied in a similar way and were significantly correlated to cell proliferation (p < 0.0001). When analysis was restricted solely 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 expression and cell proliferation, and pose the question of a link with cell differentiation.