Journal
HEMASPHERE
Volume 5, Issue 1, Pages -Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HS9.0000000000000513
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- Foundation Kinderen Kankervrij (KiKa) [KiKa-82, KiKa-219]
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Recurrent inactivating aberrations of NR3C1 have been identified in 7% of pediatric T-cell ALL patients at diagnosis, especially in early thymic progenitor-ALL patients, contributing to steroid resistance. However, there is no correlation between NR3C1 messenger RNA expression and steroid response in primary diagnostic patient samples.
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.
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