Thioimidazoline based compounds reverse glucocorticoid resistance in human acute lymphoblastic leukemia xenografts

2015 ◽  
Vol 13 (22) ◽  
pp. 6299-6312 ◽  
Author(s):  
Cara E. Toscan ◽  
Marwa Rahimi ◽  
Mohan Bhadbhade ◽  
Russell Pickford ◽  
Shelli R. McAlpine ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Glucocorticoid Therapy ◽  
Glucocorticoid Resistance ◽  
Critical Component ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Human Acute Lymphoblastic Leukemia

Glucocorticoids form a critical component of chemotherapy regimens for pediatric acute lymphoblastic leukemia and initial poor response to glucocorticoid therapy is predictive of inferior outcome.

Dysregulation of miR‐125b predicts poor response to therapy in pediatric acute lymphoblastic leukemia

2018 ◽  
Vol 120 (5) ◽  
pp. 7428-7438 ◽  
Author(s):  
Nashwa El‐Khazragy ◽  
Amal Ali Elshimy ◽  
Safaa Shawky Hassan ◽  
Safa Matbouly ◽  
Gehan Safwat ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Response To Therapy ◽  
Pediatric Acute Lymphoblastic Leukemia

Biallelic loss ofCDKN2Ais associated with poor response to treatment in pediatric acute lymphoblastic leukemia

2016 ◽  
Vol 58 (5) ◽  
pp. 1162-1171 ◽  
Author(s):  
Marcin Braun ◽  
Agata Pastorczak ◽  
Wojciech Fendler ◽  
Joanna Madzio ◽  
Bartlomiej Tomasik ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Response To Treatment ◽  
Pediatric Acute Lymphoblastic Leukemia

scholarly journals Multi-Agent Chemotherapy Overcomes Glucocorticoid Resistance Conferred by a BIM Deletion Polymorphism in Pediatric Acute Lymphoblastic Leukemia

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e103435 ◽  
Author(s):  
Sheila Xinxuan Soh ◽  
Joshua Yew Suang Lim ◽  
John W. J. Huang ◽  
Nan Jiang ◽  
Allen Eng Juh Yeoh ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Glucocorticoid Resistance ◽  
Deletion Polymorphism ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Multi Agent

Divergent Mechanisms of Glucocorticoid Resistance in Experimental Models of Pediatric Acute Lymphoblastic Leukemia

2007 ◽  
Vol 67 (9) ◽  
pp. 4482-4490 ◽  
Author(s):  
Petra S. Bachmann ◽  
Rosemary Gorman ◽  
Rachael A. Papa ◽  
Jane E. Bardell ◽  
Jette Ford ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Experimental Models ◽  
Glucocorticoid Resistance ◽  
Pediatric Acute Lymphoblastic Leukemia

PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
pp. candisc.1771.2020
Author(s):  
Jianping Li ◽  
Julia Hlavka-Zhang ◽  
Jonathan H Shrimp ◽  
Crissandra Piper ◽  
Daphne Dupere-Richer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Glucocorticoid Resistance ◽  
Pediatric Acute Lymphoblastic Leukemia

Dysregulation of miR-125b Predicts Poor Response to Therapy in Pediatric Acute Lymphoblastic Leukemia

2019 ◽  
Vol 19 ◽  
pp. S178 ◽  
Author(s):  
Nashwa El-Khazragy ◽  
Amal Ali Elshimy ◽  
Safaa Shawky Hassan ◽  
Safa Matbouly ◽  
Gehan Safwat ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Response To Therapy ◽  
Pediatric Acute Lymphoblastic Leukemia

Epigenetic silencing of BIM in glucocorticoid poor-responsive pediatric acute lymphoblastic leukemia, and its reversal by histone deacetylase inhibition

Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 3013-3022 ◽  
Author(s):  
Petra S. Bachmann ◽  
Rocco G. Piazza ◽  
Mary E. Janes ◽  
Nicholas C. Wong ◽  
Carwyn Davies ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Histone Deacetylase ◽  
Cpg Island ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Epigenetic Silencing ◽  
Glucocorticoid Resistance ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Pediatric All

Abstract Glucocorticoids play a critical role in the therapy of lymphoid malignancies, including pediatric acute lymphoblastic leukemia (ALL), although the mechanisms underlying cellular resistance remain unclear. We report glucocorticoid resistance attributable to epigenetic silencing of the BIM gene in pediatric ALL biopsies and xenografts established in immune-deficient mice from direct patient explants as well as a therapeutic approach to reverse resistance in vivo. Glucocorticoid resistance in ALL xenografts was consistently associated with failure to up-regulate BIM expression after dexamethasone exposure despite confirmation of a functional glucocorticoid receptor. Although a comprehensive assessment of BIM CpG island methylation revealed no consistent changes, glucocorticoid resistance in xenografts and patient biopsies significantly correlated with decreased histone H3 acetylation. Moreover, the histone deacetylase inhibitor vorinostat relieved BIM repression and exerted synergistic antileukemic efficacy with dexamethasone in vitro and in vivo. These findings provide a novel therapeutic strategy to reverse glucocorticoid resistance and improve outcome for high-risk pediatric ALL.

MEF2C-dysregulated pediatric T-cell acute lymphoblastic leukemia is associated withCDKN1Bdeletions and a poor response to glucocorticoid therapy

2017 ◽  
Vol 58 (12) ◽  
pp. 2895-2904 ◽  
Author(s):  
Sara Colomer-Lahiguera ◽  
Markus Pisecker ◽  
Margit König ◽  
Karin Nebral ◽  
Winfried F. Pickl ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Glucocorticoid Therapy ◽  
Cell Acute Lymphoblastic Leukemia
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