scholarly journals Anti-leukaemic effects induced by APR-246 are dependent on induction of oxidative stress and the NFE2L2/HMOX1 axis that can be targeted by PI3K and mTOR inhibitors in acute myeloid leukaemia cells

2016 ◽  
Vol 174 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Dina Ali ◽  
Dara K. Mohammad ◽  
Huthayfa Mujahed ◽  
Kerstin Jonson-Videsäter ◽  
Beston Nore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Mtor Inhibitors ◽  
Acute Myeloid

scholarly journals Oxidative Stress and X-ray Exposure Levels-Dependent Survival and Metabolic Changes in Murine HSPCs

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 11
Author(s):  
Melis Karabulutoglu ◽  
Rosemary Finnon ◽  
Lourdes Cruz-Garcia ◽  
Mark A. Hill ◽  
Christophe Badie
Keyword(s):  
Oxidative Stress ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Metabolic Changes ◽  
Target Cells ◽  
Dependent Manner ◽  
X Ray ◽  
Regulatory Systems ◽  
Dose Dependent ◽  
Acute Myeloid

Haematopoietic bone marrow cells are amongst the most sensitive to ionizing radiation (IR), initially resulting in cell death or genotoxicity that may later lead to leukaemia development, most frequently Acute Myeloid Leukaemia (AML). The target cells for radiation-induced Acute Myeloid Leukaemia (rAML) are believed to lie in the haematopoietic stem and progenitor cell (HSPC) compartment. Using the inbred strain CBA/Ca as a murine model of rAML, progress has been made in understanding the underlying mechanisms, characterisation of target cell population and responses to IR. Complex regulatory systems maintain haematopoietic homeostasis which may act to modulate the risk of rAML. However, little is currently known about the role of metabolic factors and diet in these regulatory systems and modification of the risk of AML development. This study characterises cellular proliferative and clonogenic potential as well as metabolic changes within murine HSPCs under oxidative stress and X-ray exposure. Ambient oxygen (normoxia; 20.8% O2) levels were found to increase irradiated HSPC-stress, stimulating proliferative activity compared to low oxygen (3% O2) levels. IR exposure has a negative influence on the proliferative capability of HSPCs in a dose-dependent manner (0–2 Gy) and this is more pronounced under a normoxic state. One Gy x-irradiated HSPCs cultured under normoxic conditions displayed a significant increase in oxygen consumption compared to those cultured under low O2 conditions and to unirradiated HSPCs. Furthermore, mitochondrial analyses revealed a significant increase in mitochondrial DNA (mtDNA) content, mitochondrial mass and membrane potential in a dose-dependent manner under normoxic conditions. Our results demonstrate that both IR and normoxia act as stressors for HSPCs, leading to significant metabolic deregulation and mitochondrial dysfunctionality which may affect long term risks such as leukaemia.

The acute myeloid leukaemia market

2019 ◽  
Vol 19 (4) ◽  
pp. 233-234
Author(s):  
Jorrit Schaefer ◽  
Sorcha Cassidy ◽  
Rachel M. Webster
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Acute Myeloid

Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome

2005 ◽  
Vol 44 (03) ◽  
pp. 107-117
Author(s):  
R. G. Meyer ◽  
W. Herr ◽  
A. Helisch ◽  
P. Bartenstein ◽  
I. Buchmann
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Primary Tumour ◽  
The Other ◽  
Haematopoietic Stem Cell ◽  
Other Hand ◽  
Primary Reduction ◽  
The One ◽  
Acute Myeloid

SummaryThe prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term diseasefree survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT.This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

Sign in / Sign up

Export Citation Format

Share Document