Objective: To investigate the characteristics and regulation of apoptosis in acute myeloid leukemic cells.
Methods: Flow cytometry, DNA electrophoresis and Northern blot were used to analyze the expression of bcl-X(L) before and after Vp16 treatment, and the relationships between bcl-X(L) expression and apoptotic sensitivity, clinical features and prognosis were also analyzed.
Results: Most of the leukemic cells from AML patients overexpressed bcl-X(L) mRNA. The expression of bcl-X(L) was still maintained high level after Vp16 treatment in patients with pretreatment overexpression. These patients were resistant to apoptosis, poor responsed to chemotherapy and associated with adverse prognostic features, such as high WBC counts, local leukemic infiltrations. Bone marrow cells from long-term remission AML patients and normal controls also showed bcl-X(L) downregulation after in vitro Vp16 treatment, but the apoptotic rates were lower than that in nonremissive AML.
Conclusion: Overexpression of bcl-XL played an important role in leukemogenesis and drug resistance. Downregulation of bcl-X(L) was necessary but not sufficient to initiate apoptosis.