scholarly journals A 6-Membrane Protein Gene score for prognostic prediction of cytogenetically normal acute myeloid leukemia in multiple cohorts

2020 ◽  
Vol 11 (1) ◽  
pp. 251-259 ◽  
Author(s):  
Sheng-Yan Lin ◽  
Ya-Ru Miao ◽  
Fei-Fei Hu ◽  
Hui Hu ◽  
Qiong Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Membrane Protein ◽  
Myeloid Leukemia ◽  
Protein Gene ◽  
Gene Score ◽  
Prognostic Prediction ◽  
Membrane Protein Gene ◽  
Acute Myeloid

scholarly journals A Predictor Combining Clinical and Genetic Factors for AML1-ETO Leukemia Patients

2022 ◽  
Vol 11 ◽  
Author(s):  
Min Yang ◽  
Bide Zhao ◽  
Jinghan Wang ◽  
Yi Zhang ◽  
Chao Hu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Genetic Factors ◽  
Risk Model ◽  
Core Binding Factor ◽  
Kit Mutation ◽  
Binding Factor ◽  
Prognostic Prediction ◽  
Acute Myeloid

Core Binding Factor (CBF)-AML is one of the most common somatic mutations in acute myeloid leukemia (AML). t(8;21)/AML1-ETO-positive acute myeloid leukemia accounts for 5-10% of all AMLs. In this study, we consecutively included 254 AML1-ETO patients diagnosed and treated at our institute from December 2009 to March 2020, and evaluated molecular mutations by 185-gene NGS platform to explore genetic co-occurrences with clinical outcomes. Our results showed that high KIT VAF(≥15%) correlated with shortened overall survival compared to other cases with no KIT mutation (3-year OS rate 26.6% vs 59.0% vs 69.6%, HR 1.50, 95%CI 0.78-2.89, P=0.0005). However, no difference was found in patients’ OS whether they have KIT mutation in two or three sites. Additionally, we constructed a risk model by combining clinical and molecular factors; this model was validated in other independent cohorts. In summary, our study showed that c-kit other than any other mutations would influence the OS in AML1-ETO patients. A proposed predictor combining both clinical and genetic factors is applicable to prognostic prediction in AML1-ETO patients.

scholarly journals Two-dimensional membrane protein patterns of acute myeloid leukemia cells and mature myeloid cells after various ectolabeling procedures

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 110-122
Author(s):  
JG de Jong ◽  
AW Dekker ◽  
R Kapteijn ◽  
JJ Sixma
Keyword(s):  
Acute Myeloid Leukemia ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Myeloid Leukemia ◽  
Myeloid Cells ◽  
Leukemia Cells ◽  
Two Dimensional ◽  
Protein Patterns ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Surface exposed membrane proteins of malignant cells may offer important clues about the differentiation stage of the cell or may contain proteins specific for the malignant state. We have studied the surface exposed membrane proteins of human acute myeloid leukemia cells employing the lactoperoxidase, periodate, or the neuraminidase/galactose oxidase ectolabeling procedures. One- dimensional membrane protein patterns were prepared from 20 patients, and from 19 patients, two-dimensional patterns were prepared according to OFarrell. No consistent differences in membrane proteins could be found between patients classified as M1, M2, M4, or M5 (FAB classification). A diagram of membrane proteins from acute myeloid leukemia cells subjected to two-dimensional electrophoresis could be composed from the results obtained. About 25 different membrane proteins can be indicated. Two-dimensional patterns, after the various ectolabeling procedures, were also prepared from mature myeloid cells, visualizing about 18 different membrane proteins. Comparison of these and the undifferentiated myeloid leukemia cell pattern reveals some maturation-linked or leukemia-associated differences. The most relevant proteins will be discussed, along with their association with a recently described “malignancy marker” with a molecular weight of 68,000 daltons.

scholarly journals Incorporation of long non-coding RNA expression profile in the 2017 ELN risk classification can improve prognostic prediction of acute myeloid leukemia patients

EBioMedicine ◽  
2019 ◽  
Vol 40 ◽  
pp. 240-250 ◽  
Author(s):  
Cheng-Hong Tsai ◽  
Chi-Yuan Yao ◽  
Feng-Min Tien ◽  
Jih-Luh Tang ◽  
Yuan-Yeh Kuo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Expression Profile ◽  
Myeloid Leukemia ◽  
Risk Classification ◽  
Rna Expression ◽  
Non Coding Rna ◽  
Prognostic Prediction ◽  
Long Non Coding Rna ◽  
Acute Myeloid

scholarly journals A Novel 85-Gene Expression Signature Predicts Unfavorable Prognosis in Acute Myeloid Leukemia

2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Yanli Lai ◽  
Lixia Sheng ◽  
Jiaping Wang ◽  
Miao Zhou ◽  
Guifang OuYang
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Hierarchical Clustering ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Gene Expression Signature ◽  
Gene Score ◽  
Survival Probabilities ◽  
Minimum Mean Squared Error ◽  
Acute Myeloid

Aim: Acute myeloid leukemia (AML) is a heterogeneous disorder with complex genetic basis and adverse prognosis. Cytogenetics risk, somatic mutations and gene expression profiles are important prognostic factors for AML patients. However, accurate stratification of patient prognosis remains an unsolved problem in AML. This study was to to develop a novel gene profile to accurately classify AML patients into subgroups with different survival probabilities. Methods: Survival-related genes were determined by Kaplan–Meier survival analysis and multivariate analysis using the expression and clinical data of 405 AML patients from Oregon Health & Science University (OHSU) dataset and validated in The Cancer Genome Atlas (TCGA) database. Feature selection was performed by using the Least Absolute Shrinkage and Selection Operator (LASSO) method. With the LASSO model, a prognostic 85-gene score was established and compared with 2 known gene-expression risk scores. The stratification of AML patients was performed by unsupervised hierarchical clustering of 85 gene expression levels to identify clusters of AML patients with different survival probabilities. Results: The LASSO model comprising 85 genes was considered as the optimal model based on relatively high area under curve value (0.83) and the minimum mean squared error. The 85-gene score was associated with increased mortality in AML patients. Hierarchical clustering analysis of the 85 genes revealed 3 subgroups of AML patients in the OHSU dataset. The cluster1 AML patients were associated with more female cases, higher percent of bone marrow blast cells, 85-gene score, cytogenetics risk, more frequent FLT3-ITD, DNMT3A, NP1 mutations, less frequent TP53, RUNX1 mutations, poorer overall survival than cluster2 tumors. The 85-gene score had higher AUC (0.75) than the 5-gene risk score and LSC17 score (0.74 and 0.65). Conclusions: The 85-gene score is superior to the 2 established prognostic gene signatures in the prediction of prognosis of AML patients.

scholarly journals Two-dimensional membrane protein patterns of acute myeloid leukemia cells and mature myeloid cells after various ectolabeling procedures

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 110-122 ◽  
Author(s):  
JG de Jong ◽  
AW Dekker ◽  
R Kapteijn ◽  
JJ Sixma
Keyword(s):  
Acute Myeloid Leukemia ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Myeloid Leukemia ◽  
Myeloid Cells ◽  
Leukemia Cells ◽  
Two Dimensional ◽  
Protein Patterns ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Abstract Surface exposed membrane proteins of malignant cells may offer important clues about the differentiation stage of the cell or may contain proteins specific for the malignant state. We have studied the surface exposed membrane proteins of human acute myeloid leukemia cells employing the lactoperoxidase, periodate, or the neuraminidase/galactose oxidase ectolabeling procedures. One- dimensional membrane protein patterns were prepared from 20 patients, and from 19 patients, two-dimensional patterns were prepared according to OFarrell. No consistent differences in membrane proteins could be found between patients classified as M1, M2, M4, or M5 (FAB classification). A diagram of membrane proteins from acute myeloid leukemia cells subjected to two-dimensional electrophoresis could be composed from the results obtained. About 25 different membrane proteins can be indicated. Two-dimensional patterns, after the various ectolabeling procedures, were also prepared from mature myeloid cells, visualizing about 18 different membrane proteins. Comparison of these and the undifferentiated myeloid leukemia cell pattern reveals some maturation-linked or leukemia-associated differences. The most relevant proteins will be discussed, along with their association with a recently described “malignancy marker” with a molecular weight of 68,000 daltons.

scholarly journals Epigenetics Meets Genetics in Acute Myeloid Leukemia: Clinical Impact of a Novel Seven-Gene Score

2014 ◽  
Vol 32 (6) ◽  
pp. 548-556 ◽  
Author(s):  
Guido Marcucci ◽  
Pearlly Yan ◽  
Kati Maharry ◽  
David Frankhouser ◽  
Deedra Nicolet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Expression ◽  
Prognostic Impact ◽  
Sequencing Analysis ◽  
Gene Score ◽  
Expression Levels ◽  
Acute Myeloid

PurposeMolecular risk stratification of acute myeloid leukemia (AML) is largely based on genetic markers. However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance of integrating DNA methylation and genetic information in AML.MethodsNext-generation sequencing analysis of methylated DNA identified differentially methylated regions (DMRs) associated with prognostic mutations in older (≥ 60 years) cytogenetically normal (CN) patients with AML (n = 134). Genes with promoter DMRs and expression levels significantly associated with outcome were used to compute a prognostic gene expression weighted summary score that was tested and validated in four independent patient sets (n = 355).ResultsIn the training set, we identified seven genes (CD34, RHOC, SCRN1, F2RL1, FAM92A1, MIR155HG, and VWA8) with promoter DMRs and expression associated with overall survival (OS; P ≤ .001). Each gene had high DMR methylation and lower expression, which were associated with better outcome. A weighted summary expression score of the seven gene expression levels was computed. A low score was associated with a higher complete remission (CR) rate and longer disease-free survival and OS (P < .001 for all end points). This was validated in multivariable models and in two younger (< 60 years) and two older independent sets of patients with CN-AML. Considering the seven genes individually, the fewer the genes with high expression, the better the outcome. Younger and older patients with no genes or one gene with high expression had the best outcomes (CR rate, 94% and 87%, respectively; 3-year OS, 80% and 42%, respectively).ConclusionA seven-gene score encompassing epigenetic and genetic prognostic information identifies novel AML subsets that are meaningful for treatment guidance.

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