INTRODUCTION:
In spite of the remarkable progress in basic and preclinical studies of acute myeloid leukemia (AML), the five-year survival rate of AML patients remains poor, highlighting the urgent need for novel and synergistic therapies.
Over the past decade, increased attention has been focused on identifying suitable immunotherapeutic strategies for AML, and in particular on targeting leukemic cells and their progenitors. However, the clinical outcome of patients with acute myeloid leukemia (AML) remains suboptimal, despite recent approval of new promising targeted therapies.
With the evolution of targeted AML therapies, novel agents continue to be developed with the goal to improve efficacy while minimizing toxicity.
CD123 (alpha subunit of the interleukin 3 receptor) is a cell membrane protein overexpressed in several hematologic malignancies which makes it an attractive therapeutic target.
It is composed of three extracellular domains (287 amino acids), a single-pass trans membrane domain (30 amino acids), and a short intracellular region (53 amino acids).
Upon lig and binding, the IL-3R heterodimer comprised of alpha and beta chains signals through Jak2, leading to a downstream activation of effectors that result in a net increase of cell proliferation and survival.