Revistas
Revista:
NATURE COMMUNICATIONS
ISSN:
2041-1723
Año:
2022
Vol.:
13
N°:
1
Págs.:
7619
Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis, with increased incidence in older individuals. Here we analyze the transcriptome of human HSCs purified from young and older healthy adults, as well as MDS patients, identifying transcriptional alterations following different patterns of expression. While aging-associated lesions seem to predispose HSCs to myeloid transformation, disease-specific alterations may trigger MDS development. Among MDS-specific lesions, we detect the upregulation of the transcription factor DNA Damage Inducible Transcript 3 (DDIT3). Overexpression of DDIT3 in human healthy HSCs induces an MDS-like transcriptional state, and dyserythropoiesis, an effect associated with a failure in the activation of transcriptional programs required for normal erythroid differentiation. Moreover, DDIT3 knockdown in CD34+ cells from MDS patients with anemia is able to restore erythropoiesis. These results identify DDIT3 as a driver of dyserythropoiesis, and a potential therapeutic target to restore the inefficient erythroid differentiation characterizing MDS patients. © 2022, The Author(s).
Otros (PIUNA, fundaciones, contratos…)
Título:
CARACTERIZACIÓN MOLECULAR DEL LINFOMA DIFUSO
Investigador principal:
Carlos Grande García, Maria Carla Ramirez Ruiz, María del Rocío Figueroa Mora
Fecha de inicio:
21/02/2023
Fecha fin:
21/08/2025
Importe:
89.342,00€
Otros fondos:
-