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From a 2DE-Gel Spot to Protein Function: Lesson Learned From HS1 in Chronic Lymphocytic Leukemia
Published on: October 19, 2014
High expression of Bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy
E Tóthová1, M Fricova, N Stecová
1Department of Hematology; Medical Faculty Hospital and UPJS, Kosice, 040 66 Slovakia. etothova@post.sk
Insights
High bcl-2 protein expression in acute myeloblastic leukemia (AML) correlates with lower complete remission rates. Both bcl-2 and CD34 expression are independent prognostic factors for achieving remission in AML patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- The bcl-2 protein plays a crucial role in apoptosis regulation.
- Acute myeloblastic leukemia (AML) is a heterogeneous hematologic malignancy.
- Understanding prognostic markers is vital for optimizing AML treatment strategies.
Purpose of the Study:
- To investigate the expression of bcl-2 protein in newly diagnosed AML patients.
- To correlate bcl-2 expression with French-American-British (FAB) subtypes and CD34 expression.
- To assess the relationship between bcl-2 expression and clinical outcome, specifically complete remission (CR) rates.
Main Methods:
- Flow cytometry was used to analyze bcl-2 protein expression in 67 newly diagnosed AML patients.
- Direct immunofluorescence with an anti-bcl-2 monoclonal antibody was employed.
- Results were correlated with FAB classification, CD34 expression, and CR rates.
Main Results:
- Bcl-2 expression was heterogeneous, with a mean of 81% positive cells.
- Higher bcl-2 expression percentages were observed in FAB M0 and M1 subtypes.
- Mean fluorescence index (MFI) of bcl-2 was significantly higher in M0 and M1 compared to M4 and M5 subtypes (p=0.01).
- Bcl-2 MFI significantly correlated with CD34 positivity and CD34 MFI.
- High bcl-2 expression (≥20% positive cells) was associated with a lower CR rate (40.4%) compared to low expression (<20% positive cells) (72%).
Conclusions:
- Bcl-2 protein expression is a significant factor in AML.
- High bcl-2 MFI (>16) and CD34 expression are independent prognostic factors for achieving CR in AML.
- These findings suggest that bcl-2 expression levels can aid in predicting treatment response in AML.
Abstract:
Flow cytometric expression of bcl-2 protein was analyzed in 67 newly diagnosed acute myeloblastic leukemia (AML) patients using an anti-bcl-2 monoclonal antibody by direct immunofluorescence technique and results were correlated with FAB subtype, CD34 expression and clinical outcome. The number of bcl-2+ cells in each sample was heterogenous (range, 19% to 96%), with a mean of 81%. The percentage of bcl-2+ cells was higher in M0 and M1 types according to French-American-British classification. The mean fluorescence index (MFI), expressed as the ratio of sample channel:control mean channel was significantly higher (p=0.01) in M0 (19.0) and M1 (17.6) than M4 (11.7) and M5 (8.9) cytotypes. In addition, bcl-2 MFI significantly correlated both with CD34 positivity and with CD34 MFI. High percentage expression of bcl-2 and MFI index of bcl-2 was associated with a low complete remission rate after intensive chemotherapy (40.4% in cases with 20% and more positive cells vs 72% in cases with less than 20% positive cells). By statistical analysis we also demonstrated that both bcl-2 high MFI (>16) and CD34 expression are independent prognostic factors for achieving CR in AML.
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