Latest perspectives on glucocorticoid-induced apoptosis and resistance in lymphoid malignancies

Clarisse, Dorien; Offner, Fritz; Bosscher, Karolien De

doi:10.1016/j.bbcan.2020.188430

Cited by 30 publications

(31 citation statements)

References 247 publications

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“…ALL is often treated with glucocorticoids, which regulate many physiological processes and alter the transcriptional programs of cells, such that the proliferative capacity of ALL cells is diminished and apoptosis is induced. Thus, patients whose ALL cells are sensitive to glucocorticoids have a significantly better prognosis than those whose cells are resistant to the treatment [83][84][85]. Moreover, ALL cells that are resistant to glucocorticoids have significantly higher expression levels of NLRP3 and caspase-1.…”

Section: Acute Lymphocytic Leukemia (All)mentioning

confidence: 99%

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

Urwanisch

Luciano

Horejs‐Hoeck

2021

IJMS

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Chronic inflammation contributes to the development and progression of various tumors. Especially where the inflammation is mediated by cells of the innate immune system, the NLRP3 inflammasome plays an important role, as it senses and responds to a variety of exogenous and endogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The NLRP3 inflammasome is responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 and for the induction of a type of inflammatory cell death known as pyroptosis. Overactivation of the NLRP3 inflammasome can be a driver of various diseases. Since leukemia is known to be an inflammation-driven cancer and IL-1β is produced in elevated levels by leukemic cells, research on NLRP3 in the context of leukemia has increased in recent years. In this review, we summarize the current knowledge on leukemia-promoting inflammation and, in particular, the role of the NLRP3 inflammasome in different types of leukemia. Furthermore, we examine a connection between NLRP3, autophagy and leukemia.

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Section: Acute Lymphocytic Leukemia (All)mentioning

confidence: 99%

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

Urwanisch

Luciano

Horejs‐Hoeck

2021

IJMS

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“…Gcs have been an effective component of anti-lymphoma therapies due to their anti-proliferative, pro-apoptotic and anti-angiogenic activities [ 22 ]. Synthetic Gcs, such as Dex, are routinely included in chemotherapy protocols of acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, Hodgkin’s and non-Hodgkin’s lymphoma [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…One of the fundamental physiological functions of Gcs is to oppose the effects of insulin and enhance the liver production of glucose [ 22 , 34 , 35 ]. Gcs decrease rate-limiting insulin receptor signaling molecules and reduce insulin-mediated increase in blood flow to muscles, simultaneously promoting gluconeogenesis in the liver via upregulation of enzymes tyrosine aminotransferase (TAT), glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) [ 22 , 34 , 39 ]. Activation of these mechanisms lead to a deregulated carbohydrate metabolism, hyperglycemia, and in more severe cases to steroid-induced diabetes.…”

Section: Introductionmentioning

confidence: 99%

The long winding road to the safer glucocorticoid receptor (GR) targeting therapies

et al. 2022

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Glucocorticoids (Gcs) are widely used to treat inflammatory diseases and hematological malignancies, and despite the introduction of novel anti-inflammatory and anti-cancer biologics, the use of inexpensive and effective Gcs is expected to grow. Unfortunately, chronic treatment with Gcs results in multiple atrophic and metabolic side effects. Thus, the search for safer glucocorticoid receptor (GR)-targeted therapies that preserve therapeutic potential of Gcs but result in fewer adverse effects remains highly relevant. Development of selective GR agonists/modulators (SEGRAM) with reduced side effects, based on the concept of dissociation of GR transactivation and transrepression functions, resulted in limited success, and currently focus has shifted towards partial GR agonists. Additional approach is the identification and inhibition of genes associated with Gcs specific side effects. Others and we recently identified GR target genes REDD1 and FKBP51 as key mediators of Gcs-induced atrophy, and selected and validated candidate molecules for REDD1 blockage including PI3K/Akt/mTOR inhibitors. In this review, we summarized classic and contemporary approaches to safer GR-mediated therapies including unique concept of Gcs combination with REDD1 inhibitors. We discussed protective effects of REDD1 inhibitors against Gcs–induced atrophy in skin and bone and underlined the translational potential of this combination for further development of safer and effective Gcs-based therapies.

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“…Despite its clinical importance, prolonged glucocorticoid treatment is hampered by the emergence of glucocorticoid resistance and detrimental side effects. 2 Therefore, it is crucial to optimize glucocorticoid use in IBD, which requires an improved understanding of the glucocorticoid action in IBD.…”

mentioning

confidence: 99%