Loss of erythroblasts in acute myeloid leukemia causes iron redistribution with clinical implications [article]

Marta Lopes, Tiago Duarte, Maria Jose Teles, Laura Mosteo, Sergio Chacim, Eliana Aguiar, Joana Pereira-Reis, Monica Oliveira, Andre M N Silva, Nuno Goncalves, Gabriela Martins, Isabella Kong (+10 others)
2020 bioRxiv   pre-print
Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in AML patients at diagnosis and mechanisms involved using the syngeneic MLL-AF9-induced AML mouse
more » ... ced AML mouse model. We found that AML is a disorder with a unique iron profile not associated with inflammation or transfusion and characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that leukemic blasts take up iron and that the AML-induced loss of erythroblasts is responsible for iron redistribution and an increase in TSAT. We also show that elevated TSAT at diagnosis is independently associated with increased overall survival in AML and suggest that TSAT may be a relevant prognostic marker in AML.
doi:10.1101/2020.10.26.350116 fatcat:kl2nueobojhmfkrgqjb3tg3mi4