adrenomedullin receptor
Recently Published Documents


TOTAL DOCUMENTS

57
(FIVE YEARS 1)

H-INDEX

20
(FIVE YEARS 0)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nassiba Merabet ◽  
Mohamed Jalloul Nsaibia ◽  
Quang Trinh Nguyen ◽  
Yan Fen Shi ◽  
Myriam Letourneau ◽  
...  

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1449-1449
Author(s):  
Jean-Emmanuel Sarry ◽  
Christian Recher ◽  
Clément Larrue

Abstract After intensive chemotherapy, the emergence of cells with drug resistant and/or stem cell features might explain frequent relapses and the poor outcome of patients with acute myeloid leukemia (AML). Herein, we first uncovered that the adrenomedullin receptor CALCRL is overexpressed in AML patients compared to normal cells and preferentially in the immature CD34+CD38- compartment. Then, we demonstrated its role in the maintenance of leukemic stem cell function in vivo (Figure A). Moreover, CALCRL depletion strongly affected leukemic growth in xenograft models and sensitized to chemotherapeutic agent cytarabine in vivo. Accordingly, we showed that ADM-CALCRL axis drove BCL2 pathway, cell cycle and DNA integrity in E2F1-dependent manner, and high OxPHOS status that we previously described as a feature of minimal residual disease after chemotherapy (Farge et al., 2017). Moreover, CALCRL expression predicted the response to chemotherapy in vivo in mice (n=10 Patient Derived Xenografts; Figure B) and in patients. Further, using the combination of limiting dilution assays, single cell RNA-seq analysis of primary AML samples at diagnosis and relapse and before and after transplantation in NSG mice, we revealed the pre-existence of a chemoresistant leukemic stem cell sub-population harboring a CALCRL gene signature (Figure C-D). All of these data highlight the critical role of CALCRL in stem cell function and metabolism. They also identify this receptor as a new druggable marker of chemoresistant leukemic stem cell population and a promising therapeutic target to specifically eradicate them and overcome relapse in AML. Disclosures No relevant conflicts of interest to declare.


2016 ◽  
Vol 291 (22) ◽  
pp. 11657-11675 ◽  
Author(s):  
Harriet A. Watkins ◽  
Madhuri Chakravarthy ◽  
Rekhati S. Abhayawardana ◽  
Joseph J. Gingell ◽  
Michael Garelja ◽  
...  

2015 ◽  
Vol 21 (12) ◽  
pp. 905-912 ◽  
Author(s):  
Ria Schönauer ◽  
Anette Kaiser ◽  
Cathleen Holze ◽  
Stefanie Babilon ◽  
Johannes Köbberling ◽  
...  

2015 ◽  
Vol 14 (5) ◽  
pp. 7290.2015.00003 ◽  
Author(s):  
François Harel ◽  
Xavier Levac ◽  
Quang T. Nguyen ◽  
Myriam Létourneau ◽  
Sophie Marcil ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document