High Id1 Expression Is Associated with Poor Prognosis in 237 Patients with Acute Myeloid Leukemia.

Abstract 4687

Inhibitors of differentiation (Id) or DNA binding helix-loop-helix (HLH) proteins are a group of dominant inhibitors of basic HLH transcriptional factors, which act as positive regulators of cell growth or promote excessive proliferation, and also protect cells against drug-induced apoptosis in mammalians. Recently, Id1 has been identified as a common downstream target of several constitutively activated oncogenic tyrosine kinase(TK), such as FLT3/ITD, in leukemia cells. We analyzed Id1 expression as possible prognostic factor in 237 AML patients. High Id1 expression was associated with older age(p=0.009); and with Ftl3/ITD(p=0.003). However, 61% of the patients in the group of FLT3^- AML were Id1⁺, suggesting that other TK are involved. In whole population, high Id1 expression independently predicted shorter disease free survival (DFS)(p=0.05), and overall survival (OS)(p=0.003). In the subgroup of young patients (age'60 years) with normal cytogenetic, Id1⁺ was, in multivariate analysis, associated with lower CR rates(p=0.02), shorter DFS(p=0.02) and OS(p=0.006).

In conclusion our data provides a new molecular marker for refining the risk classification of AML especially in young patients with normal cytogenetic. Id1^- patients with normal cytogenetic should be classified as favourable-risk leukemia. Id1, as a downstream target of constitutively activated TK, could be a suitable candidate for targeted therapy.