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Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML)
Abstract
The inability to undergo apoptosis is a crucial mechanism of multidrug resistance in acute myeloid leukemia (AML), and the analysis of mitochondrial apoptotic proteins may represent a significant prognostic tool to predict outcome. Bcl-2 and Bax oncoproteins were evaluated in 255 de novo AML patients (pts) by flow cytometry using an anti–bcl-2 monoclonal antibody (MoAb) and an anti-bax MoAb. The results were expressed as an index (bax/bcl-2) obtained by dividing bax mean fluorescence intensity (MFI) and bcl-2 MFI. Lower bax/bcl-2 ratio was associated with French-American-British (FAB) M0-M1 classes (P = .000 01) and CD34 more than 20% (P < .000 01). There were striking inverse correlations between CD34 or CD117 MFI and bax/bcl-2 values (r = −.40, P < .000 001 andr = −.29, P = .000 002), confirming that immaturity is consistent with this index. Moreover, lower bax/bcl-2 levels were correlated with poor-risk cytogenetics (P = .0002). A significant higher complete remission (CR) rate was found in pts with higher bax/bcl-2 levels (79% versus 45%; P = .000 01). Also, both a longer overall survival (OS) and disease-free survival (DFS) were observed in pts with higher bax/bcl-2 levels (P = .000 01 and = .019). Noteworthy, bax/bcl-2 levels accurately predicted the clinical response and outcome of pts with normal or unknown cytogenetics. Indeed, within this subset of 147 pts, higher bax/bcl-2 ratio was significantly associated both with a higher CR rate (86% versus 42%;P < .000 01) and a longer OS (P = .0016). The independent prognostic value of bax/bcl-2 ratio was confirmed in multivariate analysis. Therefore, mitochondrial oncoproteins, such as bcl-2 and bax, represent both sensitive indicators of clinical outcome and potential targets of novel proapoptotic molecules in order to circumvent chemoresistance.
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Cites
Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
Oltval, Z. N., Milliman, C. L., & Korsmeyer, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)90509-o · Cited by 6,003
Cited by
Wei, A. H., Strickland, S. A., Hou, J.-Z., Fiedler, W., Lin, T. L., Walter, R. B., Enjeti, A., Tiong, I. S., Savona, M., Lee, S., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.18.01600 · Cited by 692
Shan, F., Shao, Z., Jiang, S., & Cheng, Z. (2016) · Cancer Medicine · doi:10.1002/cam4.881 · Cited by 88
Xu, C.-L., Wang, Q.-Z., Sun, L.-M., Li, X.-M., Deng, J.-M., Li, L.-F., Zhang, J., Xu, R., & Ma, S.-P. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.09.014 · Cited by 85
Xu, C.-L., Qu, R., Zhang, J., Li, L.-F., & Ma, S.-P. (2013) · Fitoterapia · doi:10.1016/j.fitote.2013.07.009 · Cited by 84
Metadata
- Authors
- Del Poeta, G., Venditti, A., Del Principe, M. I., Maurillo, L., Buccisano, F., Tamburini, A., Cox, M. C., Franchi, A., Bruno, A., Mazzone, C., Panetta, P., Suppo, G., Masi, M., & Amadori, S.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-03-15
- Volume
- 101
- Issue
- 6
- Pages
- 2125-2131
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2150065770
- Cited by
- 340
- References
- 1
- FWCI
- 9.30
- Type
- journal article
- Language
- en
- Open access
- closed
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- Del Poeta, G., Venditti, A., Del Principe, M. I., Maurillo, L., Buccisano, F., Tamburini, A., Cox, M. C., Franchi, A., Bruno, A., Mazzone, C., Panetta, P., Suppo, G., Masi, M., & Amadori, S. (2003). Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood. https://doi.org/10.1182/blood-2002-06-1714
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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