scholarly journals A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

2015 ◽  
Vol 5 (3) ◽  
pp. e297-e297 ◽  
Author(s):  
E Saland ◽  
H Boutzen ◽  
R Castellano ◽  
L Pouyet ◽  
E Griessinger ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Xenograft Model ◽  
Chemotherapeutic Agents ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals IL-6 blockade reverses bone marrow failure induced by human acute myeloid leukemia

2020 ◽  
Vol 12 (538) ◽  
pp. eaax5104 ◽  
Author(s):  
Tian Yi Zhang ◽  
Ritika Dutta ◽  
Brooks Benard ◽  
Feifei Zhao ◽  
Raymond Yin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Failure ◽  
Xenograft Model ◽  
Erythroid Differentiation ◽  
Hematopoietic Stem ◽  
Human Acute Myeloid Leukemia ◽  
Immunocompromised Mice ◽  
Acute Myeloid

Most patients with acute myeloid leukemia (AML) die from complications arising from cytopenias resulting from bone marrow (BM) failure. The common presumption among physicians is that AML-induced BM failure is primarily due to overcrowding, yet BM failure is observed even with low burden of disease. Here, we use large clinical datasets to show the lack of correlation between BM blast burden and degree of cytopenias at the time of diagnosis. We develop a splenectomized xenograft model to demonstrate that transplantation of human primary AML into immunocompromised mice recapitulates the human disease course by induction of BM failure via depletion of mouse hematopoietic stem and progenitor populations. Using unbiased approaches, we show that AML-elaborated IL-6 acts to block erythroid differentiation at the proerythroblast stage and that blocking antibodies against human IL-6 can improve AML-induced anemia and prolong overall survival, suggesting a potential therapeutic approach.

scholarly journals Piceatannol, a Structural Analog of Resveratrol, Is an Apoptosis Inducer and a Multidrug Resistance Modulator in HL-60 Human Acute Myeloid Leukemia Cells

2021 ◽  
Vol 22 (19) ◽  
pp. 10597
Author(s):  
Kamila Siedlecka-Kroplewska ◽  
Agata Wrońska ◽  
Zbigniew Kmieć
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Myeloid Leukemia ◽  
Chemotherapeutic Agent ◽  
Chemotherapeutic Agents ◽  
Leukemia Cells ◽  
Term Survival ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Acute myeloid leukemia is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Despite recent advances in the treatment of this disease, the prognosis and overall long-term survival for patients remain poor, which drives the search for new chemotherapeutics and treatment strategies. Piceatannol, a polyphenolic compound present in grapes and wine, appears to be a promising chemotherapeutic agent in the treatment of leukemia. The aim of the present study was to examine whether piceatannol induces autophagy and/or apoptosis in HL-60 human acute myeloid leukemia cells and whether HL-60 cells are able to acquire resistance to piceatannol toxicity. We found that piceatannol at the IC90 concentration of 14 µM did not induce autophagy in HL-60 cells. However, it induced caspase-dependent apoptosis characterized by phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. Our findings also imply that HL-60 cells are able to acquire resistance to piceatannol toxicity via mechanisms related to MRP1 activity. Our results suggest that the use of piceatannol as a potential chemotherapeutic agent may be associated with the risk of multidrug resistance, warranting its use in combination with other chemotherapeutic agents.

Negative regulation of the LKB1/AMPK pathway by ERK in human acute myeloid leukemia cells

2015 ◽  
Vol 43 (7) ◽  
pp. 524-533.e1 ◽  
Author(s):  
Ichiro Kawashima ◽  
Toru Mitsumori ◽  
Yumi Nozaki ◽  
Takeo Yamamoto ◽  
Yuki Shobu-Sueki ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Negative Regulation ◽  
Leukemia Cells ◽  
Ampk Pathway ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid
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