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.
Subject(s)
Carrier Proteins/genetics , Cell Cycle Proteins , Lymphocytes/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Protein Kinases , Animals , CDC2-CDC28 Kinases , Cell Cycle , Cell Division , Cell Line , Cyclin-Dependent Kinases , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , RNA, Messenger/analysis , RabbitsABSTRACT
Four patients with lung cancer and hematological disorders occurring in different stages of the disease are presented. In three out of them cancer metastases were found prior to the discovery of the primary focus. In two patients those metastases were localized in the bone marrow resulting in the hematological picture of the myelodysplastic syndrome and osteomyelofibrosis. In one of them acute lymphoblastic leukemia developed after short-lasting remission involving the regression of bone marrow metastases of the cancer. In one patient lymph node enlargement, constitutional symptoms and laboratory signs of inflammation led to the preliminary diagnosis of Hodgkin disease. In the remaining patient acute leukemia resistant to chemotherapy developed 34 month after the diagnosis of lung cancer. Our observations point to the necessity of the through diagnosis in every case of hematologic abnormalities of unknown origin and the search of a possible underlying malignancy.
