scholarly journals High Expression Levels of X-Linked Inhibitor of Apoptosis Protein and Survivin Correlate with Poor Overall Survival in Childhood de Novo Acute Myeloid Leukemia

2004 ◽  
Vol 10 (11) ◽  
pp. 3737-3744 ◽  
Author(s):  
Ingo Tamm ◽  
Stephan Richter ◽  
Doreen Oltersdorf ◽  
Ursula Creutzig ◽  
Jochen Harbott ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
High Expression ◽  
Inhibitor Of Apoptosis ◽  
Poor Overall Survival ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Acute Myeloid

High Expression Levels of Iaps Predict Poor Overall Survival in Childhood De Novo Acute Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4396-4396
Author(s):  
Ingo Tamm ◽  
Stephan Richter ◽  
Doreen Oltersdorf ◽  
Ursula Creutzig ◽  
Jochen Harbott ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
High Expression ◽  
Prognostic Impact ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Apoptosis-related proteins are important molecules for predicting chemotherapy response and prognosis in adult acute myeloid leukemia (AML). However, data on the expression and prognostic impact of these molecules in childhood AML are rare. Using flow cytometry and western blot analysis, we therefore investigated 45 leukemic cell samples of children with de novo AML enrolled and treated within the German AML-BFM93 study for the expression of apoptosis-regulating proteins (CD95, Bcl-2, Bax, Bcl-xL, Procaspase-3, XIAP, cIAP-1, Survivin). XIAP (p<0.002) but no other apoptosis regulators showed maturation-dependent expression differences as determined by FAB morphology with the highest expression levels observed within the immature M0/1 subtypes. XIAP (p<0.01) and Bcl-xL (p<0.01) expression was lower in patients with favorable than intermediate/poor cytogenetics. After a mean follow-up of 34 months, a shorter overall survival was associated with high expression levels of XIAP {30 (n=10) vs. 41 months (n=34); p<0.05} and Survivin {27 (n=10) vs. 41 months (n=34); p<0.05}. We conclude that apoptosis-related molecules are associated with maturation stage, cytogenetic risk groups and therapy outcome in childhood de novo AML. The observed association of XIAP with immature FAB types, intermediate/poor cytogenetics and poor overall survival should be confirmed within prospective pediatric AML trials.

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

scholarly journals Higher TOX Genes Expression Is Associated With Poor Overall Survival for Patients With Acute Myeloid Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Chaofeng Liang ◽  
Yujie Zhao ◽  
Cunte Chen ◽  
Shuxin Huang ◽  
Tairan Deng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
High Mobility ◽  
The Cancer Genome Atlas ◽  
Poor Overall Survival ◽  
Training Cohort ◽  
Hmg Box ◽  
Acute Myeloid

Thymocyte selection-associated HMG box (TOX) is a transcription factor that belongs to the high mobility group box (HMG-box) superfamily, which includes four subfamily members: TOX, TOX2, TOX3, and TOX4. TOX is related to the formation of multiple malignancies and contributes to CD8+ T cell exhaustion in solid tumors. However, little is known about the role of TOX genes in hematological malignancies. In this study, we explored the prognostic value of TOX genes from 40 patients with de novo acute myeloid leukemia (AML) by quantitative real-time PCR (qRT-PCR) in a training cohort and validated the results using transcriptome data from 167 de novo AML patients from the Cancer Genome Atlas (TCGA) database. In the training cohort, higher expression of TOX and TOX4 was detected in the AML samples, whereas lower TOX3 expression was found. Moreover, both the training and validation results indicated that higher TOX2, TOX3, and TOX4 expression of AML patients (3-year OS: 0% vs. 37%, P = 0.036; 3-year OS: 4% vs. 61%, P < 0.001; 3-year OS: 0% vs. 32%, P = 0.010) and the AML patients with highly co-expressed TOX, TOX2, TOX4 genes (3-year OS: 0% vs. 25% vs. 75%, P = 0.001) were associated with poor overall survival (OS). Interestingly, TOX2 was positively correlated with CTLA-4, PD-1, TIGIT, and PDL-2 (rs = 0.43, P = 0.006; rs = 0.43, P = 0.006; rs = 0.56, P < 0.001; rs = 0.54, P < 0.001). In conclusion, higher expression of TOX genes was associated with poor OS for AML patients, which was related to the up-regulation of immune checkpoint genes. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TOX genes in novel targeted therapies for AML.

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

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

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