Study of Survivin and X-Linked Inhibitor of Apoptosis Protein (XIAP) Genes in Acute Myeloid Leukemia (AML)

2012 ◽  
Vol 18 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Azza Mostafa Ibrahim ◽  
Iman Maher Mansour ◽  
Manal Michel Wilson ◽  
Doha Abdel-Hamid Mokhtar ◽  
Amani Mohamed Helal ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Acute Myeloid

scholarly journals Phase I/II Trial of AEG35156 X-Linked Inhibitor of Apoptosis Protein Antisense Oligonucleotide Combined With Idarubicin and Cytarabine in Patients With Relapsed or Primary Refractory Acute Myeloid Leukemia

2009 ◽  
Vol 27 (28) ◽  
pp. 4741-4746 ◽  
Author(s):  
Aaron D. Schimmer ◽  
Elihu H. Estey ◽  
Gautam Borthakur ◽  
Bing Z. Carter ◽  
Gary J. Schiller ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Phase I ◽  
Antisense Oligonucleotide ◽  
Myeloid Leukemia ◽  
Complete Response ◽  
Inhibitor Of Apoptosis ◽  
High Dose ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Acute Myeloid

Purpose X-linked inhibitor of apoptosis protein (XIAP) is an inhibitor of caspases 3 and 9 which are overexpressed in acute myeloid leukemia (AML) and may contribute to chemoresistance. We report on a phase I/II trial of the XIAP antisense oligonucleotide AEG35156 in combination with reinduction chemotherapy. Patients and Methods Twenty-four patients with rapidly relapsed or refractory AML were treated with escalating doses of AEG35156 (12 to 250 mg/m2) as an intravenous solution over 2 hours and 32 patients were treated with the highest planned dose of 350 mg/m2 in combination with idarubicin and high-dose cytarabine reinduction chemotherapy. Correlative studies were conducted to determine the effects of AEG35156 on levels of XIAP mRNA. Results Knockdown of XIAP mRNA during treatment increased with the dose of the antisense. All patients who received 350 mg/m2 of AEG35156 had higher than 30% target knockdown with a median maximal knockdown of 90% (range, 48% to 100%). The overall response rate was higher among the patients receiving the highest dose of AEG35156. In this group, 15 (47%) of 32 patients achieved complete response (CR)/CR with incomplete platelet count recovery (CRp) compared with only one (4%) of 24 receiving 12 to 250 mg/m2 AEG35156. Among the patients receiving 350 mg/m2 of AEG35156 in combination with chemotherapy, 10 (91%) of 11 who were refractory to a single induction chemotherapy regimen achieved CR/CRp after reinduction with AEG35156 and chemotherapy. AEG35156 was well tolerated save for two cases of peripheral neuropathy in patients receiving multiple doses of AEG35156. Conclusion At the highest dose tested, AEG35156 knocks down its target and appears very effective when combined with chemotherapy in patients with AML refractory to a single induction regimen.

Prognostic value of inhibitor of apoptosis protein family expression in patients with acute myeloid leukemia

2015 ◽  
Vol 56 (9) ◽  
pp. 2529-2535 ◽  
Author(s):  
Agnieszka Pluta ◽  
Agnieszka Wierzbowska ◽  
Barbara Cebula-Obrzut ◽  
Piotr Pluta ◽  
Konrad Stępka ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Protein Family ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Acute Myeloid

The Therapeutical Potential of a Novel Pterocarpanquinone LQB-118 to Target Inhibitor of Apoptosis Proteins in Acute Myeloid Leukemia Cells

2013 ◽  
Vol 13 (2) ◽  
pp. 341-351 ◽  
Author(s):  
Flaviana R. de Souza Reis ◽  
Fernanda C. Casal de Faria ◽  
Carolina P. Castro ◽  
Paloma S. de Souza ◽  
Flavia da Cunha Vasconcelos ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Proteins ◽  
Acute Myeloid Leukemia Cells ◽  
Apoptosis Proteins ◽  
Acute Myeloid

scholarly journals MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide

2019 ◽  
Vol 27 (9) ◽  
pp. 1035-1042 ◽  
Author(s):  
Zhiguo Wang ◽  
Zehui Fang ◽  
Runzhang Lu ◽  
Hongli Zhao ◽  
Tiejun Gong ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Arsenic Trioxide ◽  
Myeloid Leukemia ◽  
Luciferase Activity ◽  
Cell Growth Inhibition ◽  
Apoptosis Protein ◽  
Acute Myeloid Leukemia Cells ◽  
Leukemia Treatment ◽  
Novel Target ◽  
Acute Myeloid

Although arsenic trioxide (ATO) is a well-known antileukemic drug used for acute promyelocytic leukemia treatment, the development of ATO resistance is still a big challenge. We previously reported that microRNA-204 (miR-204) was involved in the regulation of acute myeloid leukemia (AML) cell apoptosis, but its role in chemoresistance is poorly understood. In the present study, we showed that miR-204 was significantly increased in AML cells after ATO treatment. Interestingly, the increased miR-204 level that was negatively correlated with ATO induced the decrease in cell viability and baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression. Overexpression of miR-204 potentiated ATO-induced AML cell growth inhibition and apoptosis. Furthermore, miR-204 directly targets to the 3′-UTR of BIRC6. Upregulation of miR-204 decreased BIRC6 luciferase activity and expression, which subsequently enhanced the expression of p53. Restoration of BIRC6 markedly reversed the effect of miR-204 on the regulation of AML cell sensitivity to ATO. Taken together, our study demonstrates that miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis. miR-204 represents a novel target of ATO, and upregulation of miR-204 may be a useful strategy to improve the efficacy of ATO in AML treatment.

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