Cyclin E overexpression in relapsed adult acute lymphoblastic leukemias of B-cell lineage.
Using Western blot analysis, we examined cyclin E and cyclin A protein levels in 19 patients with acute lymphoblastic leukemia ([ALL] 15 B-ALL and four T-ALL). Whereas normal, nonproliferating peripheral blood mononuclear cells (PBMCs) expressed low levels of the 50-kD cyclin E, ALL blasts in the peripheral blood, although showing low-level or no proliferation as judged by FACS/cell-cycle analysis and cyclin A protein levels, expressed high levels of cyclin E, with a mean value similar to that of the proliferating Burkitt's lymphoma cell line, Akata. The accumulation of a protein shown to shorten the G1 phase of the cell cycle, cyclin E, in growth-delayed leukemic blasts may reflect the malignant status of these cells. Before treatment, B-ALL cells expressed predominantly the 50-kD cyclin E. T-ALL samples displayed the 50-kD cyclin E protein and a smaller, approximately 43-kD cyclin E species. In paired B-ALL samples taken before treatment and at relapse, we found a significant overexpression of the 50-kD protein in relapsed samples (P < .006), plus the presence of up to four additional smaller-molecular-weight species of cyclin E, illustrating clear diagnosis versus relapse differences. Cyclin E expression in ALL blasts may correlate to the relative malignant status of the cells, with higher protein levels reflecting a more advanced stage of the disease and a greater potential to proliferate under permissive conditions.
Scuderi
R
R
Division of Medicine, Karolinska Hospital, Stockholm, Sweden.
Palucka
K A
KA
Pokrovskaja
K
K
Björkholm
M
M
Wiman
K G
KG
Pisa
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002453:Cell Cycle; D016213:Cyclins / Q000096:biosynthesis*; D018572:Disease-Free Survival; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D014408:Biomarkers, Tumor; D016213:Cyclins; D009363:Neoplasm Proteins