Loss of erythroblasts in acute myeloid leukemia causes iron redistribution with clinical implications.

Abstract

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 patients with AML at diagnosis and explored the mechanisms involved using the syngeneic MLL-AF9-induced AML mouse model. We found that AML is a disorder with a unique iron profile, not associated with inflammation or transfusion, 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 the AML-induced loss of erythroblasts is responsible for iron redistribution and increased TSAT. We also show that AML progression is delayed in mouse models of systemic iron overload and that elevated TSAT at diagnosis is independently associated with increased overall survival in AML. We suggest that TSAT may be a relevant prognostic marker in AML.

• Authors: Marta Lopes, Tiago L Duarte, Maria J Teles, Laura Mosteo, Sérgio Chacim, Eliana Aguiar, Joana Pereira-Reis, Mónica Oliveira, André M N Silva, Nuno Gonçalves, Gabriela Martins, Isabella Y Kong, Magnus Zethoven, Stephin Vervoort, Sandra Martins, Miguel Quintela, Edwin D Hawkins, Fernanda Trigo, João T Guimarães, José M Mariz, Graça Porto, Delfim Duarte
• Journal: Blood advances (Blood Adv) Vol. 5 Issue 16 Pg. 3102-3112 (08 24 2021) ISSN: 2473-9537 [Electronic] United States
• PMID: 34402883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Transferrin
• Iron

Topics

• Anemia
• Animals
• Erythroblasts
• Humans
• Iron
• Leukemia, Myeloid, Acute
• Mice
• Transferrin