Molecular Insight into Iron Homeostasis of Acute Myeloid Leukemia Blasts

Abstract

Acute myeloid leukemia (AML) remains a disease of gloomy prognosis despite intense efforts to understand its molecular foundations and to find efficient treatments. In search of new characteristic features of AML blasts, we first examined experimental conditions supporting the amplification of hematological CD34+ progenitors ex vivo. Both AML blasts and healthy progenitors heavily depended on iron availability. However, even if known features, such as easier engagement in the cell cycle and amplification factor by healthy progenitors, were observed, multiplying progenitors in a fully defined medium is not readily obtained without modifying their cellular characteristics. As such, we measured selected molecular data including mRNA, proteins, and activities right after isolation. Leukemic blasts showed clear signs of metabolic and signaling shifts as already known, and we provide unprecedented data emphasizing disturbed cellular iron homeostasis in these blasts. The combined quantitative data relative to the latter pathway allowed us to stratify the studied patients in two sets with different iron status. This categorization is likely to impact the efficiency of several therapeutic strategies targeting cellular iron handling that may be applied to eradicate AML blasts.