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

Jordy C.G. Van Der Zwet, Willem Smits, Jessica G.C.A.M. Buijs-Gladdines, Rob Pieters, Jules P.P. Meijerink

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)E513
JournalHemaSphere
Volume5
Issue number1
DOIs
Publication statusPublished - 21 Jan 2021

Fingerprint

Dive into the research topics of 'Recurrent NR3C1 Aberrations at First Diagnosis Relate to Steroid Resistance in Pediatric T-Cell Acute Lymphoblastic Leukemia Patients'. Together they form a unique fingerprint.

Cite this