scholarly journals Construction of a novel ferroptosis-related gene signature for predicting prognosis and immune microenvironment in acute myeloid leukemia

2021 ◽  
Author(s):  
Xianbo Huang ◽  
De Zhou ◽  
Xiujin Ye ◽  
Jie Jin
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Model ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Low Risk ◽  
Cox Regression Analysis ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy that strongly correlates with poor clinical outcomes. Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death which plays an important role in various human cancers. Nevertheless, the prognostic significance and functions of ferroptosis-related genes (FRGs) in AML have not received sufficient attention. The aim of this article was to evaluate the association between FRGs levels and AML prognosis using publicly available RNA-sequencing datasets. The univariate Cox regression analysis identified 20 FRGs that correlate with patient overall survival. The LASSO Cox regression model was used to construct a prognostic 12-gene risk model using a TCGA cohort, and internal and external validation proved the signature efficient. The 12-FRGs signature was then used to assign patients into high- and low-risk groups, with the former exhibiting markedly reduced overall survival, compared to the low-risk group. ROC curve analysis verified the predictive ability of the risk model. Functional analysis showed that immune status and drug sensitivity differed between the 2 risk groups. In summary, FRGs is a promising candidate biomarker and therapeutic target for AML.

scholarly journals High Expression of PXN Predicts a Poor Prognosis in Acute myeloid leukemia

2021 ◽  
Author(s):  
xinwen zhang ◽  
Hao Xiong ◽  
Jialin Duan ◽  
Xiaomin Chen ◽  
Yang Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Receive Treatment ◽  
To Receive ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is one of the common malignant diseases of hematopoietic system. Paxillin ( PXN ) is an important part of focal adhesions (FAs), which is related to the poor prognosis of many kinds of malignant tumors. However, no research has focused on the expression of PXN in AML. We aimed to investigate the expression of PXN in AML and its prognostic significance. Methods: Using GEPIA and UALCAN database to analyze the expression of PXN in AML patients and its prognostic significance. Bone marrow samples of newly diagnosed AML patients were collected to extract RNA, and qRT-PCR was used to detect the expression of PXN . The prognosis was followed up. Chi-square test was used to analyze the relationship between PXN expression and clinical laboratory characteristics. Kaplan-Meier analysis was used to draw survival curve, and Cox regression analysis was used to analyze the independent factors affecting the prognosis of patients with AML. The co-expression genes of PXN were analyzed by LinkedOmics to explore its biological significance in AML. Results: Kaplan-Meier analysis showed that the overall survival time of AML patients was related to whether to receive treatment and PXN expression(P<0.05). COX regression analysis showed that whether to receive treatment (HR=0.227，95%CI=0.075-0.689， P =0.009) and high expression of PXN (HR=4.484，95%CI=1.449-13.889， P =0.009) were independent poor prognostic factors in patients with AML. Conclusion: PXN is highly expressed in AML patient, and high PXN expression is an indicator of poor prognosis in AML patient.

scholarly journals Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia

2022 ◽  
Vol 12 ◽  
Author(s):  
Ying Song ◽  
Shufang Tian ◽  
Ping Zhang ◽  
Nan Zhang ◽  
Yan Shen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Model ◽  
Risk Groups ◽  
Low Risk ◽  
Functional Enrichment ◽  
Great Promise ◽  
Cox Regression Analysis ◽  
Blood Disorder ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a clonal malignant proliferative blood disorder with a poor prognosis. Ferroptosis, a novel form of programmed cell death, holds great promise for oncology treatment, and has been demonstrated to interfere with the development of various diseases. A range of genes are involved in regulating ferroptosis and can serve as markers of it. Nevertheless, the prognostic significance of these genes in AML remains poorly understood. Transcriptomic and clinical data for AML patients were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Univariate Cox analysis was performed to identify ferroptosis-related genes with prognostic value, and the least absolute shrinkage and selection operator (LASSO) algorithm and stepwise multivariate Cox regression analysis were utilized to optimize gene selection from the TCGA cohort (132 samples) for model construction. Tumor samples from the GEO database (136 samples and 104 samples) were used as validation groups to estimate the predictive performance of the risk model. Finally, an eight-gene prognostic signature (including CHAC1, CISD1, DPP4, GPX4, AIFM2, SQLE, PGD, and ACSF2) was identified for the prediction of survival probability and was used to stratify AML patients into high- and low-risk groups. Survival analysis illustrated significantly prolonged overall survival and lower mortality in the low-risk group. The area under the receiver operating characteristic curve demonstrated good results for the training set (1-year: 0.846, 2-years: 0.826, and 3-years: 0.837), which verified the accuracy of the model for predicting patient survival. Independent prognostic analysis indicated that the model could be used as a prognostic factor (p ≤ 0.001). Functional enrichment analyses revealed underlying mechanisms and notable differences in the immune status of the two risk groups. In brief, we conducted and validated a novel ferroptosis-related prognostic model for outcome prediction and risk stratification in AML, with great potential to guide individualized treatment strategies in the future.

A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 971-978 ◽  
Author(s):  
Christoph Röllig ◽  
Christian Thiede ◽  
Martin Gramatzki ◽  
Walter Aulitzky ◽  
Heinrich Bodenstein ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Model ◽  
Cox Model ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Npm1 Mutation ◽  
Prognostic Groups ◽  
Acute Myeloid

Abstract We present an analysis of prognostic factors derived from a trial in patients with acute myeloid leukemia older than 60 years. The AML96 trial included 909 patients with a median age of 67 years (range, 61-87 years). Treatment included cytarabine-based induction therapy followed by 1 consolidation. The median follow-up time for all patients is 68 months (5.7 years). A total of 454 of all 909 patients reached a complete remission (50%). Five-year overall survival (OS) and disease-free survival were 9.7% and 14%, respectively. Multivariate analyses revealed that karyotype, age, NPM1 mutation status, white blood cell count, lactate dehydrogenase, and CD34 expression were of independent prognostic significance for OS. On the basis of the multivariate Cox model, an additive risk score was developed that allowed the subdivision of the largest group of patients with an intermediate-risk karyotype into 2 groups. We are, therefore, able to distinguish 4 prognostic groups: favorable risk, good intermediate risk, adverse intermediate risk, and high risk. The corresponding 3-year OS rates were 39.5%, 30%, 10.6%, and 3.3%, respectively. The risk model allows further stratification of patients with intermediate-risk karyotype into 2 prognostic groups with implications for the therapeutic strategy. This study was registered at www.clinicaltrials.gov as #NCT00180115.

scholarly journals Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 118 (15) ◽  
pp. 4188-4198 ◽  
Author(s):  
Sebastian Schwind ◽  
Guido Marcucci ◽  
Jessica Kohlschmidt ◽  
Michael D. Radmacher ◽  
Krzysztof Mrózek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Hox Genes ◽  
De Novo ◽  
Prognostic Significance ◽  
The Impact ◽  
Favorable Group ◽  
Acute Myeloid

AbstractLow MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene–embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.

scholarly journals Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5824-5831 ◽  
Author(s):  
Ana Flávia Tibúrcio Ribeiro ◽  
Marta Pratcorona ◽  
Claudia Erpelinck-Verschueren ◽  
Veronika Rockova ◽  
Mathijs Sanders ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Gene Expression Signature ◽  
Mutation Status ◽  
Cox Regression Analysis ◽  
Prognostic Effect ◽  
Or Gene ◽  
Acute Myeloid

Abstract The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3Amutant AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3Awild-type AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3Amutant AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3Awild-type AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

scholarly journals Expression Levels of Human Equilibrative Nucleoside Transporter 1 and Deoxycytidine Kinase Enzyme as Prognostic Factors in Patients with Acute Myeloid Leukemia Treated with Cytarabine

Chemotherapy ◽  
2016 ◽  
Vol 61 (6) ◽  
pp. 313-318 ◽  
Author(s):  
Myrna Candelaria ◽  
Carmen Corrales-Alfaro ◽  
Olga Gutiérrez-Hernández ◽  
José Díaz-Chavez ◽  
Juan Labardini-Méndez ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Performance Status ◽  
Deoxycytidine Kinase ◽  
Nucleoside Transporter ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Equilibrative Nucleoside Transporter ◽  
Acute Myeloid

Background: Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter (hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug. Methods: AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival. Results: Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival. Conclusions: These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients.

Mitoxantrone, Etoposide, and Intermediate-Dose Cytarabine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia : Single-Center Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4007-4007
Author(s):  
Hwa Jung Sung ◽  
Eui Bae Kim ◽  
Se Ryeon Lee ◽  
Hee Yun Seo ◽  
Kyong Hwa Park ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Relapsed Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Background: The results of salvage chemotherapy for patient with refractory or relapsed acute myeloid leukemia(AML) have been generally disappointing with low response rates and occasional long-term survivors in most studies. Since therapeutic failure seems to be inevitable in the great majority of these patients, development of more effective salvage therapy is warranted. Recent approaches to the treatment of previously treated AML generally involved the use of cytarabine in intermediate or high-dose alone or in association with new intercalating agents, such as amsacrine, mitoxantrone or idarubicin, etoposide, or asparaginase. Methods: A single course of mitoxantrone 6 mg/m2 intravenous (IV) bolus, etoposide 80 mg/m2 IV for 1 hour, and cytarabine (Ara-C) 1g/m2 IV for 6 hours daily for 6 days (MEC), has been proposed as a salvage regimen. Between October 1998 and May 2005, thirty refractory/relapsed AML patients have been treated by MEC salvage chemotherapy. Twenty two patients were in relapse and eight patients were refractory after conventional induction chemotherapy including cytarabine and idarubicin or mitoxantrone. Two patient were in relapse after allogenous hematopoietic stem cell transplantation(SCT). Results: Complete remission(CR) was obtained in 12 of 30 patients(40%) and 3 of 30(10%) died during salvage treatment: 2 due to intracranial hemorrhage and 1 due to fungemia sepsis. After CR achievement, 5 patients received consolidation chemotherapy. Two patients with an HLA-identical sibling donor underwent allogeneic SCT, and one patient received autologous SCT. Severe myelosuppression was observed in all patients resulting in fever or documented infections in 90% of patients. Nonhematologic toxicity was minimal. At the time of analysis, 9 of 11 patients who achieved CR have relapsed. Median disease-free survival was 12 months. Median overall survival was 13.5 months. There were only two longterm remitters. Several clinicolaboratory and treatment-related variables were analyzed to determine their prognostic significance for CR achievement, duration of CR, overall survival. Conclusions: Our results suggest that MEC combination chemotherapy might induce CR in a patient with refractory or relapsed AML, although new agents or new therapeutic strategies should be required for long term remission.

scholarly journals A three-gene signature might predict prognosis in patients with acute myeloid leukemia

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xin Zhu ◽  
Qian Zhao ◽  
Xiaoyu Su ◽  
Jinming Ke ◽  
Yunyun Yi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Transcription Factor ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Risk Group ◽  
White Blood Cells ◽  
Gene Signature ◽  
Low Risk ◽  
Acute Myeloid

Abstract The identification of effective signatures is crucial to predict the prognosis of acute myeloid leukemia (AML). The investigation aimed to identify a new signature for AML prognostic prediction by using the three-gene expression (octamer-binding transcription factor 4 (OCT4), POU domain type 5 transcription factor 1B (POU5F1B) and B-cell-specific Moloney murine leukemia virus integration site-1 pseudogene 1 (BMI1P1). The expressions of genes were obtained from our previous study. Only the specimens in which three genes were all expressed were included in this research. A three-gene signature was constructed by the multivariate Cox regression analyses to divide patients into high-risk and low-risk groups. Receiver operating characteristic (ROC) analysis of the three-gene signature (area under ROC curve (AUC) = 0.901, 95% CI: 0.821–0.981, P&lt;0.001) indicated that it was a more valuable signature for distinguishing between patients and controls than any of the three genes. Moreover, white blood cells (WBCs, P=0.004), platelets (PLTs, P=0.017), percentage of blasts in bone marrow (BM) (P=0.011) and complete remission (CR, P=0.027) had significant differences between two groups. Furthermore, high-risk group had shorter leukemia-free survival (LFS) and overall survival (OS) than low-risk group (P=0.026; P=0.006), and the three-gene signature was a prognostic factor. Our three-gene signature for prognosis prediction in AML may serve as a prognostic biomarker.

Sign in / Sign up

Export Citation Format

Share Document