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

Autor: Jordy C. G. van der Zwet, Willem Smits, Jessica G. C. A. M. Buijs-Gladdines, Rob Pieters, Jules P. P. Meijerink
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: HemaSphere, Vol 5, Iss 1, p e513 (2021)
Druh dokumentu: article
ISSN: 2572-9241
00000000
DOI: 10.1097/HS9.0000000000000513
Popis: 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.
Databáze: Directory of Open Access Journals
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