Investigators publish new data in the report "Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia."

12-14-2006

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 and cross-talk between STPs could activate multiple downstream effectors and this could negate the effect of single-target inhibition," investigators in the United States report.

"The frequency of concurrent activation of multiple STPs in AML and the prognostic relevance of STP activation in AML are unknown. STP protein expression (PKCalpha, ERK2, pERK2, AKT, and pAKT) was measured by Western blot in samples from 188 patients with newly diagnosed, untreated AML. In univariate and multivariate analysis high levels of PKCalpha, ERK, pERK, and pAKT, but not AKT, were adverse factors for survival as was the combination variable PKCalpha-ERK2&pERK2-pAKT. Survival progressively decreased as the number of activated pathways increased. Patients were more likely to have none or all 3 pathways activated than was predicted based on the frequency of individual pathway activation, strongly suggesting that cross-activation occurred. Simultaneous activation of multiple STPs is common in AML and has a progressively worse adverse effect on prognosis," wrote S.M. Kornblau and colleagues, University of Texas, M.D. Anderson Cancer Center.

The researchers concluded: "It is thus likely that only combinations of agents that target the multiply activated STPs will be beneficial for patients with AML."

Kornblau and colleagues published their study in Blood (Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. Blood, 2006;108(7):2358-65).

For additional information, contact S.M. Kornblau, University of Texas M D Anderson Cancer Center, Section of Molecular Hematology and Therapy, Unit 448, 1515 Holcombe Blvd., Houston, TX 77030 U.S.