Talia Velasco-Hernandez, Juan L Trincado, Meritxell Vinyoles, Adria Closa, Alba Martínez-Moreno, Francisco Gutiérrez-Agüera, Oscar Molina, Virginia C Rodríguez-Cortez, Pau Ximeno-Parpal, Narcís Fernández-Fuentes, Paolo Petazzi, Sergi Beneyto-Calabuig, Lars Velten, Paola Romecin, Raquel Casquero, Fernando Abollo-Jiménez, Rafael D de la Guardia, Patricia Lorden, Alex Bataller, Hélène Lapillonne, Ronald W Stam, Susana Vives, Montserrat Torrebadell, Jose L Fuster, Clara Bueno, Jean-Emmanuel Sarry, Eduardo Eyras, Holger Heyn, Pablo Menéndez
Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy-resistant leukemia stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling maintains cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hypothesis that hypoxia contributes to the chemoresistance of AML-LSCs and may represent a therapeutic target to sensitize AML-LSCs to chemotherapy. Here, we identify HIFhigh and HIFlow specific AML subgroups (inv(16)/ t (8;21) and MLLr, respectively) and provide a comprehensive single-cell expression atlas of 119,000 AML cells and AML-LSCs in paired diagnostic-relapse samples from these molecular subgroups...
February 2024: HemaSphere