Association Of Immunophenotype With Expression Of Topoisomerase Ii Alpha And Beta In Adult Acute Myeloid Leukemia

Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase II (topo II) isoforms, topo II alpha and topo II beta. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo II alpha and topo II beta by RT-PCR and its relationship to immunophenotype (IP) and outcomes. Treatment outcomes were analyzed by logistic or Cox regression. In 211 patients, available for analysis, topo II alpha expression was significantly lower than topo II beta (P < 0.0001). In contrast to topo II alpha, topo II beta was significantly associated with blast percentage in marrow or blood (P = 0.0001), CD7 (P = 0.01), CD14 (P < 0.0001) and CD54 (P < 0.0001). Event free survival was worse for CD56-negative compared to CD56-high (HR = 1.9, 95% CI [1.0-3.5], p = 0.04), and overall survival was worse for CD-15 low as compared to CD15-high (HR = 2.2, 95% CI [1.1-4.2], p = 0.02). Ingenuity pathway analysis indicated topo II beta and immunophenotype markers in a network associated with cell-to-cell signaling, hematological system development/function and inflammatory response. Topo II beta expression reflects disease biology of highly proliferative disease and distinct IP but does not appear to be an independent variable influencing outcome in adult AML patients treated with anthracycline-based therapy.