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Clinical Cancer Research Vol. 5, 1758-1766, July 1999
© 1999 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

The Prognostic Impact of BCL2 Protein Expression in Acute Myelogenous Leukemia Varies with Cytogenetics1

Steven M. Kornblau2, Peter F. Thall, Zeev Estrov, Monica Walterscheid, Shilpen Patel, Alexandra Theriault, Michael J. Keating, Hagop Kantarjian, Elihu Estey and Michael Andreeff

Departments of Molecular Hematology and Therapy [S. M. K., M. W., S. P., A. T., M. A.], Leukemia [M. J. K., H. K., E. E.], Biostatistics [P. F. T.], and Bioimmunotherapy [Z. E.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095

BCL2 protein exerts an antiapoptotic effect on cells and decreases chemosensitivity. To determine whether BCL2 expression is prognostic of patient outcome in acute myelogenous leukemia (AML), we measured its level in 198 newly diagnosed, untreated AML patients by Western blotting using whole-cell lysates from low-density peripheral blood cells. BCL2 expression was not associated with the percentage of blasts (R2 = 0.10), French-American-British classification type, or cytogenetic abnormality. Smoothed martingale residual plots indicated that high BCL2 protein level was an adverse prognostic factor for patients with either favorable or intermediate prognosis cytogenetics [FIPC; inv(16), t(8:21), t(15:17), or diploid or insufficient metaphases] but was a favorable prognostic factor for patients with unfavorable prognosis cytogenetics (UC; -5, -7, +8, 11q23, Ph1, or miscellaneous changes). Patients with FIPC and high BCL2 (highest quartile) had a significantly shorter median survival (78 weeks versus not reached; P = 0.009) than did those with lower (lower three quartiles) levels of BCL2. Among those with UC, as BCL2 level decreased from the fourth quartile to the third or the combined first and second quartiles, the median survival decreased (from 94 to 45 or 17 weeks, respectively; P = 0.003). Lower expression of BCL2 in UC was associated with shorter remission duration (P = 0.05). In multivariate analyses performed using either overall or event-free survival as the end point, for either all patients or within either cytogenetic subgroup, BCL2 level was an independent prognostic factor. Similar analysis revealed that BCL2 level was an independent predictor of remission duration for UC patients as well. These data suggest that BCL2 is involved differently in different types (favorable versus unfavorable) of AML and that therapeutic strategies aimed at modulating BCL2 function may be more likely to work in patients with favorable cytogenetic abnormalities.




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Copyright © 1999 by the American Association for Cancer Research.