Recurrent NR3C1 Aberrations at First Diagnosis Relate to Steroid Resistance in Pediatric T‐Cell Acute Lymphoblastic Leukemia Patients

The glucocorticoid receptor NR3C1 is essential for steroid‐induced apoptosis, and deletions of this gene have been recurrently identified at disease relapse for acute lymphoblastic leukemia (ALL) patients. Here, we demonstrate that recurrent NR3C1 inactivating aberrations—including deletions, missen...

Full description

Saved in:
Bibliographic Details
Published in:HemaSphere 2021-01, Vol.5 (1), p.e513-n/a
Main Authors: Zwet, Jordy C. G., Smits, Willem, Buijs‐Gladdines, Jessica G. C. A. M., Pieters, Rob, Meijerink, Jules P. P.
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The glucocorticoid receptor NR3C1 is essential for steroid‐induced apoptosis, and deletions of this gene have been recurrently identified at disease relapse for acute lymphoblastic leukemia (ALL) patients. Here, we demonstrate that recurrent NR3C1 inactivating aberrations—including deletions, missense, and nonsense mutations—are identified in 7% of pediatric T‐cell ALL patients at diagnosis. These aberrations are frequently present in early thymic progenitor‐ALL patients and relate to steroid resistance. Functional modeling of NR3C1 aberrations in pre‐B ALL and T‐cell ALL cell lines demonstrate that aberrations decreasing NR3C1 expression are important contributors to steroid resistance at disease diagnosis. Relative NR3C1 messenger RNA expression in primary diagnostic patient samples, however, does not correlate with steroid response.
ISSN:2572-9241
2572-9241
DOI:10.1097/HS9.0000000000000513