Differential expression of cell proliferation regulatory proteins in B‐ and T‐lineage acute lymphoblastic leukaemias

Abstract

In order to better understand the molecular background of differences between the clinical picture of T- and B-lineage ALLs, we studied the expression of several proteins involved in the regulation of cell proliferation in bone marrow blast cells from 30 cases of previously untreated acute lymphoblastic leukaemia (ALL); 14 cases were T- and 16 B-cell lineage ALLs. We studied several cyclin-dependent kinases (cdk1, cdk2, cdk4, cdk6) and cyclins (cyclin A, cyclin B1, cyclin D3 and cyclin E). We also studied proliferating cell nuclear antigen (PCNA) and Bcl-2 expression, the latter protein known to be involved in the prolonged survival of B-lineage ALL blasts. Proteins obtained from cell lysates were resolved on polyacrylamide gel followed by immunodetection and densitometry of specific bands. Expression of cdk1 and PCNA, markers of proliferative activity, was significantly higher in T- than in B-lineage ALL. Cdk6, which was highly correlated to PCNA, was also higher in T-cell ALL. In contrast, B-lineage ALL displayed a higher expression of anti-apoptotic protein Bcl-2. We hypothesize that those particularities may reflect differential roles of cell multiplication and apoptosis in the neoplastic proliferation of B- and T-lineage ALL.

Cyclin E in normal and neoplastic cell cycles

“…Many cancers overexpress cyclin E protein or mRNA including carcinomas (breast, lung, cervix, endometrium, gastrointestinal tract), lymphoma, leukemia, sarcomas and adrenocortical tumors (Wolowiec et al, 1996;Yasui et al, 1996a, b;Iida et al, 1997;Molendini et al, 1998;Dong et al, 2000;Fukuse et al, 2000;Erlanson and Landberg, 2001;Muller-Tidow et al, 2001;Schraml et al, 2003;Tissier et al, 2004). Several mechanisms deregulate cyclin E expression in tumors.…”

Cyclins and Cell Cycle Control in Cancer and Disease

“…152 The abundance of the cyclin E transcript and protein is increased in carcinomas of the lung, gastrointestinal tract, and breast in addition to lymphomas and leukemias. [153][154][155][156][157][158][159] Increased cyclin E expression occurs in 18% to 22% of breast cancers and has been used as a prognostic marker. 160 A low molecular weight hyperactive version of cyclin E exists in breast cancer and is associated with very poor prognosis.…”

True

“…17 Lymphoblast populations were divided into four categories: (1) early early pre-B (CD10 − ) ALL (six cases), (2) early pre-B (CD10 + ) (33 cases) and pre-B-ALL (IgM + ) (three cases), (3) B ALL (one case) and (4) T-ALL (15 cases).…”