scholarly journals LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia

2021 ◽  
Vol 38 (4) ◽  
pp. 264-272
Author(s):  
Hong Zhai ◽  
Junting Zhao ◽  
Juan Pu ◽  
Pan Zhao ◽  
Jin Wei
Keyword(s):  
Acute Myeloid Leukemia ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Induced Apoptosis ◽  
Acute Myeloid

scholarly journals Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Hao Wang ◽  
Yu-chen Liu ◽  
Cheng-ying Zhu ◽  
Fei Yan ◽  
Meng-zhen Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Signaling Pathway ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Complete Response ◽  
Dependent Manner ◽  
Induce Cell Cycle Arrest ◽  
Anthracycline Resistance ◽  
Acute Myeloid ◽  
Resistant Cells

Abstract Background Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. Methods In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. Results Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. Conclusion Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

Proteasome inhibitor-induced apoptosis in acute myeloid leukemia: A correlation with the proteasome status

2010 ◽  
Vol 34 (4) ◽  
pp. 498-506 ◽  
Author(s):  
Mariette Matondo ◽  
Marie-Pierre Bousquet-Dubouch ◽  
Nathalie Gallay ◽  
Sandrine Uttenweiler-Joseph ◽  
Christian Recher ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Proteasome Inhibitor ◽  
Myeloid Leukemia ◽  
Induced Apoptosis ◽  
Acute Myeloid

scholarly journals Selective targeting of NAMPT by KPT-9274 in acute myeloid leukemia

2019 ◽  
Vol 3 (3) ◽  
pp. 242-255 ◽  
Author(s):  
Shaneice R. Mitchell ◽  
Karilyn Larkin ◽  
Nicole R. Grieselhuber ◽  
Tzung-Huei Lai ◽  
Matthew Cannon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Tumor Development ◽  
Xenograft Model ◽  
Nicotinamide Phosphoribosyltransferase ◽  
P21 Activated Kinase ◽  
Induced Apoptosis ◽  
Acute Myeloid

Abstract Treatment options for acute myeloid leukemia (AML) remain extremely limited and associated with significant toxicity. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the generation of NAD+ and a potential therapeutic target in AML. We evaluated the effect of KPT-9274, a p21-activated kinase 4/NAMPT inhibitor that possesses a unique NAMPT-binding profile based on in silico modeling compared with earlier compounds pursued against this target. KPT-9274 elicited loss of mitochondrial respiration and glycolysis and induced apoptosis in AML subtypes independent of mutations and genomic abnormalities. These actions occurred mainly through the depletion of NAD+, whereas genetic knockdown of p21-activated kinase 4 did not induce cytotoxicity in AML cell lines or influence the cytotoxic effect of KPT-9274. KPT-9274 exposure reduced colony formation, increased blast differentiation, and diminished the frequency of leukemia-initiating cells from primary AML samples; KPT-9274 was minimally cytotoxic toward normal hematopoietic or immune cells. In addition, KPT-9274 improved overall survival in vivo in 2 different mouse models of AML and reduced tumor development in a patient-derived xenograft model of AML. Overall, KPT-9274 exhibited broad preclinical activity across a variety of AML subtypes and warrants further investigation as a potential therapeutic agent for AML.

DT-13 induced apoptosis and promoted differentiation of acute myeloid leukemia cells by activating AMPK-KLF2 pathway

2020 ◽  
Vol 158 ◽  
pp. 104864 ◽  
Author(s):  
Chengqiang Wang ◽  
Hui He ◽  
Gen Liu ◽  
Haoyue Ma ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Acute Myeloid Leukemia Cells ◽  
Induced Apoptosis ◽  
Acute Myeloid

scholarly journals Functional Toll-Like Receptors (TLRs) Are Expressed by a Majority of Primary Human Acute Myeloid Leukemia Cells and Inducibility of the TLR Signaling Pathway Is Associated with a More Favorable Phenotype

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 973 ◽  
Author(s):  
Annette K. Brenner ◽  
Øystein Bruserud
Keyword(s):  
Acute Myeloid Leukemia ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Receptor Expression ◽  
Cytokine Secretion ◽  
Toll Like Receptors ◽  
Tlr Signaling ◽  
General Response ◽  
Tlr Signaling Pathway ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous disease with regard to biological characteristics and receptor expression. Toll-like receptors (TLRs) are upstream to the transcription factor NFκB and part of the innate immune system. They are differentially expressed on AML blasts, and during normal hematopoiesis they initiate myeloid differentiation. In this study, we investigated the response upon TLR stimulation in an AML cohort (n = 83) by measuring the increase of NFκB-mediated cytokine secretion. We observed that TLR4 is readily induced in most patients, while TLR1/2 response was more restricted. General response to TLR stimulation correlated with presence of nucleophosmin gene mutations, increased mRNA expression of proteins, which are part of the TLR signaling pathway and reduced expression of transcription-related proteins. Furthermore, signaling via TLR1/2 appeared to be linked with prolonged patient survival. In conclusion, response upon TLR stimulation, and especially TLR1/2 induction, seems to be part of a more favorable phenotype, which also is characterized by higher basal cytokine secretion and a more mature blast population.

scholarly journals The pan-Bcl-2 inhibitor obatoclax promotes differentiation and apoptosis of acute myeloid leukemia cells

2020 ◽  
Vol 38 (6) ◽  
pp. 1664-1676
Author(s):  
Małgorzata Opydo-Chanek ◽  
Iwona Cichoń ◽  
Agnieszka Rak ◽  
Elżbieta Kołaczkowska ◽  
Lidia Mazur
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Apoptotic Pathway ◽  
Acute Myeloid Leukemia Cells ◽  
Induced Apoptosis ◽  
Acute Myeloid

Summary One of the key features of acute myeloid leukemia (AML) is the arrest of differentiation at the early progenitor stage of myelopoiesis. Therefore, the identification of new agents that could overcome this differentiation block and force leukemic cells to enter the apoptotic pathway is essential for the development of new treatment strategies in AML. Regarding this, herein we report the pro-differentiation activity of the pan-Bcl-2 inhibitor, obatoclax. Obatoclax promoted differentiation of human AML HL-60 cells and triggered their apoptosis in a dose- and time-dependent manner. Importantly, obatoclax-induced apoptosis was associated with leukemic cell differentiation. Moreover, decreased expression of Bcl-2 protein was observed in obatoclax-treated HL-60 cells. Furthermore, differentiation of these cells was accompanied by the loss of their proliferative capacity, as shown by G0/G1 cell cycle arrest. Taken together, these findings indicate that the anti-AML effects of obatoclax involve not only the induction of apoptosis but also differentiation of leukemic cells. Therefore, obatoclax represents a promising treatment for AML that warrants further exploration.

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