The role of reactive oxygen species in differentiation of acute myeloid leukemia

2016 ◽  
Author(s):  
Chung-fan Lam
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Acute Myeloid

scholarly journals Critical Role of Lama4 for Hematopoiesis Regeneration and Acute Myeloid Leukemia Progression

Blood ◽  
2021 ◽  
Author(s):  
Huan Cai ◽  
Makoto Kondo ◽  
Lakshmi Sandhow ◽  
Pingnan Xiao ◽  
Anne-Sofie Johansson ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Bm Niche ◽  
Acute Myeloid

Impairement of normal hmatopoiesis and leukemia progression are two well-linked processes during leukemia development and controlled by the bone marrow (BM) niche. Extracellular matrix proteins including laminin are important BM niche components. However, their role in hematopoiesis regeneration and leukemia is unknown. Laminin α4 (Lama4), a major receptor-binding chain of several laminins, is altered in BM niches in mice with acute myeloid leukemia (AML). So far, the impact of Lama4 on leukemia progression remains unknown. We here report that Lama4 deletion in mice resulted in impaired hematopoiesis regeneration following irradiation-induced stress, which is accompanied with altered BM niche composition and inflammation. Importantly, in a transplantation-induced MLL-AF9 AML mouse model, we demonstrate accelerated AML progression and relapse in Lama4-/-mice. Upon AML exposure, Lama4-/- mesenchymal stem cells (MSCs) exhibited dramatic molecular alterations including upregulation of inflammatory cytokines that favor AML growth. Lama4-/- MSCs displayed increased anti-oxidant activities and promoted AML stem cell proliferation and chemoresistance to cytarabine, which was accompanied by increased mitochondrial transfer from the MSCs to AML cells and reduced reactive oxygen species in AML cells in vitro. Similarly, we detected lower levels of reactive oxygen species in AML cells from Lama4-/- mice post-cytarabine treatment. Notably, LAMA4 inhibition or knockdown in human MSCs promoted human AML cell proliferation and chemoprotection. Together, our study for the first time demonstrates a critical role of Lama4 in impeding AML progression and chemoresistance. Targeting Lama4 signaling pathways may offer potential new therapeutic options for AML.

OSU-A9, an indole-3-carbinol derivative, induces cytotoxicity in acute myeloid leukemia through reactive oxygen species-mediated apoptosis

2013 ◽  
Vol 86 (10) ◽  
pp. 1430-1440 ◽  
Author(s):  
Li-Yuan Bai ◽  
Jing-Ru Weng ◽  
Chang-Fang Chiu ◽  
Chia-Yung Wu ◽  
Su-Peng Yeh ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Acute Myeloid

Knockdown of Stromal Interaction Molecule 1 (STIM1) Suppresses Acute Myeloid Leukemia Cell Line Survival Through Inhibition of Reactive Oxygen Species Activities

2021 ◽  
Author(s):  
Eman Salem Algariri ◽  
Rabiatul Basria S. M. N. Mydin ◽  
Emmanuel Jairaj Moses ◽  
Simon Imakwu Okekpa ◽  
Nur Arzuar Abdul Rahim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Myeloid Leukemia ◽  
Cell Line ◽  
Therapeutic Target ◽  
Myeloid Leukemia ◽  
Oxygen Species ◽  
Down Regulation ◽  
Potential Therapeutic Target ◽  
Acute Myeloid

Abstract Stromal interaction molecule 1 (STIM1) is a critical regulator of calcium homeostasis through store-operated calcium entry (SOCE) and recently considered a potential therapeutic target for cancer. However, the role of STIM1 in acute myeloid leukemia (AML) remains unclear. The present study investigates the role of STIM1 in AML cell line (THP-1) proliferation and survival and its effect on reactive oxygen species (ROS) activities. Dicer-substrate siRNA (dsiRNA) - mediated STIM1 knockdown inhibited the THP-1 cells proliferation and colony formation ability. Further observation on ROS profile showed a significant reduction in the ROS level, which was associated with a significant down-regulation of NOX2 and protein kinase C (PKC). Furthermore, STIM1 knockdown exhibited significant down-regulation of Akt, KRAS, and MAPK which are critical proliferative and survival pathway-related genes. This study unveiled the importance of STIM1 in the regulation of AML cells proliferation and survival which could be through maintaining ROS at level keeping the proliferative and survival pathways at an active state. These findings represent STIM1 as a potential therapeutic target for AML treatment.

scholarly journals Reactive Oxygen Species Drive Proliferation in Acute Myeloid Leukemia via the Glycolytic Regulator PFKFB3

2019 ◽  
Vol 80 (5) ◽  
pp. 937-949 ◽  
Author(s):  
Andrew J. Robinson ◽  
Goitseone L. Hopkins ◽  
Namrata Rastogi ◽  
Marie Hodges ◽  
Michelle Doyle ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Acute Myeloid
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