The prognostic impact of BCL2 protein expression in acute myelogenous leukemia varies with cytogenetics

BCL2 protein exerts an antiapoptotic effect on cells and decreases chemosen sitivity. To determine whether BCL2 expression is prognostic of patient out come in acute myelogenous leukemia (AML), we measured its level in 198 newl y diagnosed, untreated AML patients by Western blotting using whole-cell ly sates from low-density peripheral blood cells. BCL2, expression was not ass ociated with the percentage of blasts (R-2 = 0.10), French-American-British classification type, or cytogenetic abnormality. Smoothed martingale resid ual plots indicated that high BCL2 protein level was an adverse prognostic factor for patients with either favorable or intermediate prognosis cytogen etics [FIPC; inv(16), t(8:21), t(15:17), or diploid or insufficient metapha ses] but was a favorable prognostic factor for patients with unfavorable pr ognosis cytogenetics (UC; -5, -7, +8, 11q23, Ph-1, 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 t hose 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 comb ined 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 wa s associated with shorter remission duration (P = 0.05), In multivariate an alyses performed using either overall or event-free survival as the end poi nt, for either all patients or within either cytogenetic subgroup, BCL2 lev el was an independent prognostic factor. Similar analysis revealed that BCL 2 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 w ith favorable cytogenetic abnormalities.