scholarly journals A Simple-to-Use Nomogram for Predicting Survival in Children with Acute Myeloid Leukemia

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Feng Jiang ◽  
Xiang Yu ◽  
Chuyan Wu ◽  
Ming Wang ◽  
Ke Wei ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Model ◽  
Cox Regression ◽  
Chromosomal Abnormalities ◽  
Web Based ◽  
Cox Regression Analysis ◽  
Predictive Variables ◽  
Target Database ◽  
Acute Myeloid

Background. The research analyzed a group of patients to develop a statistical nomogram and a web-based survival rate predictor for the comprehensive estimate of the overall survival (OS) of children with acute myeloid leukemia. Methods. Between 1999 to 2015, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to evaluate and randomly divide 440 children diagnosed with AML into the population of training ( n = 309 ) and validation ( n = 131 ). The analysis of Lasso Cox was used to identify separate predictive variables. We have used essential forecasting considerations to construct a nomogram and a web-based calculator focused on Cox regression analysis. Nomogram validation was tested through discrimination and calibration. Results. Compared to the multivariate training cohort models, a nomogram integrating gender, age of diagnose, WBC at diagnosis, bone marrow leukemic blast percentage, and chromosomal abnormalities [ t (8; 21), inv(16)] were designed for the prediction of OS. We also developed a predictive survival nomogram and a web-based calculator. C-indexes validated internally and checked externally were 0.747 and 0.716. The calibration curves have shown that the nomogram might accurately forecast 3-year and 5-year OS. Conclusions. A nomogram effectively predicts survival in children with AML. This prognostic model can be used in clinical practice.

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.

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 Rebound Thrombocytosis following Induction Chemotherapy Is an Independent Predictor of a Good Prognosis in Acute Myeloid Leukemia Patients Attaining First Complete Remission

2015 ◽  
Vol 134 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Umit Yavuz Malkan ◽  
Gursel Gunes ◽  
Ayse Isik ◽  
Eylem Eliacik ◽  
Sezgin Etgul ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Recovery Time ◽  
Cox Regression ◽  
De Novo ◽  
Statistical Significance ◽  
Good Prognosis ◽  
Platelet Recovery ◽  
Cox Regression Analysis ◽  
Acute Myeloid

There are very few data about the relationship between acute myeloid leukemia (AML) prognosis and bone marrow recovery kinetics following chemotherapy. In this study, we aimed to assess the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in the postchemotherapy period for newly diagnosed AML patients. De novo AML patients diagnosed between October 2002 and December 2013 were evaluated retrospectively. One hundred patients were suitable for inclusion. Cox regression analysis using need for reinduction chemotherapy as a stratification parameter revealed RT as the only parameter predictive of OS, with borderline statistical significance (p = 0.06, OR = 7; 95% CI 0.92-53), and it was the only parameter predictive of DFS (p = 0.024, OR = 10; 95% CI 1.3-75). In order to understand whether RT or RN was related to a better marrow capacity or late consolidation, we considered neutrophil recovery time and platelet recovery time and nadir-first consolidation durations in all patients in the cohort. Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients. To our knowledge, this is the first study to report a correlation between RT/RN and prognosis in AML.

scholarly journals m6A-Related lncRNAs Affect Tumor Immune Microenvironment And Prognosis In Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Fangmin Zhong ◽  
Fangyi Yao ◽  
Ying Cheng ◽  
Jing Liu ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Risk Scores ◽  
In Vitro Assays ◽  
Immune Microenvironment ◽  
Cox Regression Analysis ◽  
Tumor Immune Microenvironment ◽  
The Relationship ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a complex hematologic malignancy. Survival rate of AML patients is low. N6-methyladenosine (m6A) and long-chain non-coding RNAs (lncRNAs) play important roles in AML tumorigenesis and progression. However, the relationship between lncRNAs and biological characteristics of AML, as well as how lncRNAs influence the prognosis of AML patients, remain unclear. In this study, we identified m6A-related lncRNAs, and analyzed their roles and prognostic values in AML. m6A-related lncRNAs associated with patient prognosis were screened using univariate Cox regression analysis, followed by systematic analysis of the relationship between these genes and AML clinicopathologic and biologic characteristics. Furthermore, we examined the characteristics of tumor immune microenvironment (TIME) using different IncRNA clustering models. Using LASSO regression, we identified the risk signals related to prognosis of AML patients. We then constructed and verified a risk model based on m6A-related lncRNAs for independent prediction of overall survival in AML patients. Our results indicate that risk scores, calculated based on risk-related signaling, were related to the clinicopathologic characteristics of AML and level of immune infiltration. Finally, we examined the expression level of TRAF3IP2-AS1 in patient samples through real-time polymerase chain reaction analysis and in GEO datasets, and we identified SRSF10 as a regulator of TRAF3IP2-AS1 through in vitro assays. Our study shows that m6A-related lncRNAs, evaluated using the risk prediction model, can potentially be used to predict prognosis and design immunotherapy in AML patients.

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 Prognosis and Characterization of Immune Microenvironment in Acute Myeloid Leukemia Through Identification of an Autophagy-Related Signature

2021 ◽  
Vol 12 ◽  
Author(s):  
Denggang Fu ◽  
Biyu Zhang ◽  
Shiyong Wu ◽  
Yinghua Zhang ◽  
Jingwu Xie ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Regression Analysis ◽  
High Risk ◽  
Signaling Pathways ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Prognostic Predictor ◽  
Risk Patients ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has an unfavorable outcome and a high rate of relapse. Autophagy plays a vital role in the development of and therapeutic responses to leukemia. This study identifies a potential autophagy-related signature to monitor the prognoses of patients of AML. Transcriptomic profiles of AML patients (GSE37642) with the relevant clinical information were downloaded from Gene Expression Omnibus (GEO) as the training set while TCGA-AML and GSE12417 were used as validation cohorts. Univariate regression analyses and multivariate stepwise Cox regression analysis were respectively applied to identify the autophagy-related signature. The univariate Cox regression analysis identified 32 autophagy-related genes (ARGs) that were significantly associated with the overall survival (OS) of the patients, and were mainly rich in signaling pathways for autophagy, p53, AMPK, and TNF. A prognostic signature that comprised eight ARGs (BAG3, CALCOCO2, CAMKK2, CANX, DAPK1, P4HB, TSC2, and ULK1) and had good predictive capacity was established by LASSO–Cox stepwise regression analysis. High-risk patients were found to have significantly shorter OS than patients in low-risk group. The signature can be used as an independent prognostic predictor after adjusting for clinicopathological parameters, and was validated on two external AML sets. Differentially expressed genes analyzed in two groups were involved in inflammatory and immune signaling pathways. An analysis of tumor-infiltrating immune cells confirmed that high-risk patients had a strong immunosuppressive microenvironment. Potential druggable OS-related ARGs were then investigated through protein–drug interactions. This study provides a systematic analysis of ARGs and develops an OS-related prognostic predictor for AML patients. Further work is needed to verify its clinical utility and identify the underlying molecular mechanisms in AML.

scholarly journals Identification of the 7-lncRNA Signature as a Prognostic Biomarker for Acute Myeloid Leukemia

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Chun-yu Liu ◽  
Hui-hui Guo ◽  
Hai-xia Li ◽  
Ying Liang ◽  
Cong Tang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Cox Regression ◽  
Cumulative Risk ◽  
Risk Scores ◽  
Sequencing Data ◽  
The Public ◽  
Target Database ◽  
Acute Myeloid

A lot of evidence has emphasized the function of long noncoding RNAs (lncRNAs) in tumors’ development and progression. Nevertheless, there is still a lack of lncRNA biomarkers that can predict the prognosis of acute myeloid leukemia (AML). Our goal was to develop a lncRNA marker with prognostic value for the survival of AML. AML patients’ RNA sequencing data as well as clinical characteristics were obtained from the public TARGET database. Then, differentially expressed lncRNAs were identified in female and male AML samples. By adopting univariate and multivariate Cox regression analyses, AML patients’ survival was predicted by a seven-lncRNA signature. It was found that 95 abnormal expressed lncRNAs existed in AML. Then, the analysis of multivariate Cox regression showed that, among them, 7 (LINC00461, RP11-309M23.1, AC016735.2, RP11-61I13.3, KIAA0087, RORB-AS1, and AC012354.6) had an obvious prognostic value, and according to their cumulative risk scores, these 7 lncRNA signatures could independently predict the AML patients’ overall survival. Overall, the prognosis of AML patients could be predicted by a reliable tool, that is, seven-lncRNA prognostic signature.

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