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HDAC7 is a major contributor in the pathogenesis of infant t(4;11) proB acute lymphoblastic leukemia

Abstract: Infants diagnosed of proB-cell acute lymphoblastic leukemia (proB ALL) presenting t(4;11) chromosomal rearrangement are at high risk of disease progression and fatal outcome. This specific subtype of pediatric leukemia represents a challenge in leukemia research, given the difficulties in reproducing the disease in vivo. However, the understanding of mechanisms leading to proper lymphocyte generation may become of high utility in gaining insights into the pathogenesis of this malignancy. Here, we report that the low expression of HDAC7, a master transcriptional regulator in B lymphocyte differentiation, worsens the prognosis of proB ALL patients, regardless of the MLL gene status. Among t(4;11) proB ALL infants, those with high expression of HDAC7 display an improved survival, partially mediated by the repression of oncogenes and chemoresistance markers, such as ASNS enzyme, which eventually lead to impairment in the proliferation of t(4;11) proB ALL cells through the induction of apoptosis. Moreover, RNA sequencing of HDAC7-overexpressing t(4;11) proB ALL cells revealed that ectopic HDAC7 induces a transcriptomic signature closer to that of healthy B-cell progenitors. In summary, our findings highlight the potential of HDAC7 as a prognosis factor in high-risk proB ALL and open new therapeutic avenues for proB ALL infants by restoring HDAC7 expression.

 Fuente: Leukemia . 2020 Dec 1.

Editorial: Nature Publishing Group

 Año de publicación: 2020

Nº de páginas: 26

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41375-020-01097-x

ISSN: 0887-6924,1476-5551

Proyecto español: SAF2017-87990-R

Url de la publicación: https://doi.org/10.1038/s41375-020-01097-x

Autores/as

BARRIOS, ORIOL DE

GALARAS, ALEXANDROS

TRINCADO, JUAN L.

AZAGRA, ALBA

COLLAZO, OLGA

MELER, AINARA

ANTONIO MANUEL AGRAZ DOBLAS

BUENO, CLARA

BALLERINI, PAOLA

CAZZANIGA, GIOVANNI

STAM, RONALD W.

LORENZO, PAOLA DE

VALSECCHI, MARIA GRAZIA

HATZIS, PANTELIS

MENÉNDEZ, PABLO

PARRA, MARIBEL