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Apoptosis induction in fludarabine resistant malignant B-1 cells by G2-M cell cycle arrest
1Department of Pathology and Laboratory Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
Abstract:
A malignant B-1 cell line from a mouse model of CLL was resistant to fludarabine, but could be induced to undergo apoptosis by mitotic spindle inhibitors, colcemid or nocodazole, which blocked these cells in the G2-M phases of cell cycle prior to apoptosis induction. Bax mRNA levels increased with relative constitutive expression of bcl-2 mRNA levels. The mRNA levels of B-cell-specific-activator-protein (BSAP) decreased with colcemid treatment. This study shows that mitotic spindle inhibitors can induce apoptosis in fludarabine-resistant malignant B-1 cells by altering levels of bax/ bcl-2 ratio and BSAP which play different roles in cell cycle regulation and apoptosis induction.
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