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

Overview

Journal Hemasphere

Publisher Wiley

Specialty Hematology

Date 2020 Dec 28

PMID 33364552

Citations 7

Authors

Jordy C G Van der Zwet

Willem Smits

Jessica G C A M Buijs-Gladdines

Rob Pieters

Jules P P Meijerink

Affiliations

Soon will be listed here.

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 messenger RNA expression in primary diagnostic patient samples, however, does not correlate with steroid response.

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