Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia

摘要: Deregulation of signal transduction pathways (STPs) may promote leukemogenesis by conferring cell proliferation and survival advantages in acute myelogenous leukemia (AML). Several agents targeting STPs are under development; however, redundancy cross-talk between could activate multiple downstream effectors this negate the effect single-target inhibition. The frequency concurrent activation AML prognostic relevance STP unknown. protein expression (PKCα, ERK2, pERK2, AKT, pAKT) was measured Western blot samples from 188 patients with newly diagnosed, untreated AML. In univariate multivariate analysis high levels PKCα, ERK, pERK, pAKT, but not were adverse factors for as combination variable PKCα-ERK2&pERK2-pAKT. Survival progressively decreased number activated increased. Patients more likely to have none or all 3 than predicted based on individual pathway activation, strongly suggesting that cross-activation occurred. Simultaneous is common has a worse prognosis. It thus only combinations target multiply will be beneficial