scholarly journals Comprehensive Analysis of the Expression and Prognosis for Signal Transducer and Activator of Transcription Family of Genes in Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Tong Qin ◽  
Yunli Shao ◽  
Hongmian Zhao
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Predictive Biomarker ◽  
Signal Transducer ◽  
Lasso Regression ◽  
Expression Levels ◽  
Normal Tissues ◽  
Immunotherapy Target ◽  
Selection Operator ◽  
Acute Myeloid

Abstract BackgroundIn recent years, it has become clear that signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. However, the expression level, genetic variation, molecular mechanism, and biological function of different STATs in acute myeloid leukemia (AML) and its relationship with prognosis and immune infiltration in patients with AML have not been fully elucidated.ResultsWe found that the expression levels of STAT1, STAT2, STAT4, and STAT6 were higher in AML than in normal tissues, whereas the expression levels of STAT3, STAT5A, and STAT5B were lower in the former than in the latter. Survival analysis revealed that high transcription level of STAT6 was associated with low overall survival (OS) in patients with AML. Conversely, high STAT5B level predicted superior OS in these patients. Cox multivariate analysis as well as least absolute shrinkage and selection operator (LASSO) regression screening showed that STAT5B expression is a good independent prognostic factor of OS. The functions of STAT5B are mainly related to the occurrence, development and microenvironment of AML. We also discovered that the expression of STAT5B was significantly correlated with immune infiltrates in AML.ConclusionsSTAT5B may be used as a novel predictive biomarker and immunotherapy target for AML patients.

scholarly journals Comprehensive analysis of expression and prognosis for signal transducer and activator of transcription family in acute myeloid leukemia

2021 ◽  
Author(s):  
Tong Qin ◽  
Yunli Shao ◽  
Hongmian Zhao
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Predictive Biomarker ◽  
Signal Transducer ◽  
Lasso Regression ◽  
Expression Levels ◽  
Normal Tissues ◽  
Immunotherapy Target ◽  
Selection Operator ◽  
Acute Myeloid

Abstract In recent years, it has become clear that signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. However, the expression level, genetic variation, molecular mechanism, and biological function of different STATs in acute myeloid leukemia (AML) and its relationship with prognosis and immune infiltration in AML have not been fully elucidated. We found that the expression levels of STAT1, STAT2, STAT4, and STAT6 were higher in AML than in normal tissues, whereas the expression levels of STAT3, STAT5A, and STAT5B were lower in the former than in the latter. Survival analysis revealed that high STAT5B level predicted superior OS in these patients. Cox multivariate analysis as well as least absolute shrinkage and selection operator (LASSO) regression screening showed that STAT5B expression is a good independent prognostic factor of OS. The functions of STAT5B are mainly related to the occurrence, development and microenvironment of AML. We also discovered that the expression of STAT5B was significantly correlated with immune infiltrates in AML. In summary, our research demonstrates that STAT5B may be used as a novel predictive biomarker and immunotherapy target for AML patients.

scholarly journals Decitabine shows anti-acute myeloid leukemia potential via regulating the miR-212-5p/CCNT2 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 1013-1023
Author(s):  
Lina Xing ◽  
Jinhai Ren ◽  
Xiaonan Guo ◽  
Shukai Qiao ◽  
Tian Tian
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Myeloid Leukemia ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Proliferation And Apoptosis ◽  
Polymerase Chain ◽  
The Relationship ◽  
Acute Myeloid

AbstractPrevious research has revealed the involvement of microRNA-212-5p (miR-212-5p) and cyclin T2 (CCNT2) in acute myeloid leukemia (AML). However, whether the miR-212-5p/CCNT2 axis is required for the function of decitabine in AML has not been well elucidated. Quantitative reverse transcription-polymerase chain reaction was used to examine enrichment of miR-212-5p. The relationship between CCNT2 and miR-212-5p was verified by the luciferase reporter assay. Cell apoptosis was evaluated by flow cytometry and western blot. CCK-8 assay was performed to determine cell viability. Decitabine significantly repressed cell viability, while promoted cell apoptosis. Meanwhile, the expression levels of cyclinD1, CDK4, and Bcl-2 were suppressed in cells with decitabine exposure, but Bax and caspase-3 expression levels were upregulated. Besides, miR-212-5p upregulation had the similar function with decitabine in AML cell proliferation and apoptosis. Subsequently, restoration of CCNT2 attenuated miR-212-5p overexpression-induced effects in Kasumi-1 and SKNO-1 cells. In addition, miR-212-5p depletion reversed decitabine-induced CCNT2 downregulation. The miR-212-5p/CCNT2 axis had an implication in the anti-leukemic effect of decitabine in AML.

Clinical impact of KMT2C and SPRY4 expression levels in intensively treated younger adult acute myeloid leukemia patients

2017 ◽  
Vol 99 (6) ◽  
pp. 544-552 ◽  
Author(s):  
Sabine Kayser ◽  
Maximilian Feszler ◽  
Julia Krzykalla ◽  
Matthias Schick ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Clinical Impact ◽  
Expression Levels ◽  
Acute Myeloid

scholarly journals A proteomic approach to understand the clinical significance of acute myeloid leukemia-derived extracellular vesicles reflecting essential characteristics of leukemia

2020 ◽  
pp. mcp.RA120.002169
Author(s):  
Ka-Won Kang ◽  
Hyoseon Kim ◽  
Woojune Hur ◽  
Jik-han Jung ◽  
Su Jin Jeong ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Extracellular Vesicle ◽  
The Cancer Genome Atlas ◽  
Enzyme Linked Immunosorbent Assay ◽  
Expression Levels ◽  
Proteomic Approach ◽  
Cancer Genome Atlas ◽  
Acute Myeloid

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. Enzyme-linked immunosorbent assay results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML-derived EVs could reflect essential leukemia biology.

scholarly journals Significance of PARP1 expression levels in patients with acute myeloid leukemia

2018 ◽  
Vol 29 ◽  
pp. ix87 ◽  
Author(s):  
H. Pashaiefar ◽  
M. Yaghmaie ◽  
J. Tavakkoly-Bazzaz ◽  
S.H. Ghaffari ◽  
K. Alimoghaddam ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Expression Levels ◽  
Acute Myeloid

scholarly journals Identification and Validation of STAT6 as a Prognostic and Predictive Biomarker in Acute Myeloid Leukemia

2020 ◽  
Vol Volume 13 ◽  
pp. 11165-11176
Author(s):  
Wei Liu ◽  
Feiyue Zhu ◽  
Jiazhuo Yan ◽  
Yi Liu ◽  
Cong Chen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Predictive Biomarker ◽  
Acute Myeloid

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.

Analysis of HOXA5 and HOXB3 Expression Complements Conventional Cytogenetic Analysis in Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2388-2388
Author(s):  
Damian P.J. Finnegan ◽  
Vivien M. Hodges ◽  
Alexander Thompson ◽  
Michael F. Quinn ◽  
Mervyn Humphries ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Expression Profiling ◽  
Cytogenetic Analysis ◽  
Myeloid Leukemia ◽  
Response To Treatment ◽  
Gene Rearrangements ◽  
Expression Levels ◽  
Conventional Cytogenetic Analysis ◽  
Favorable Group ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous group of hematological malignancies with individual cases showing wide variations in response to treatment. Pre-treatment karyotype analysis may be used to stratify cases into one of three prognostic classes: favorable, intermediate or adverse. Favorable karyotypes, t(15;17), t(8;21) and inv(16), are associated with the presence PML-RARα, AML1-ETO and CBFβ-MYH11 gene rearrangements respectively. The adverse cytogenetic abnormalities are monosomy 5, monosomy 7, deletion of chromosome 5q, abnormalities of chromosome 3q and a complex karyotype. All remaining abnormalities are associated with an intermediate prognosis. Approximately 5–10% of cases cannot be stratified due to failure of cytogenetic analysis. Cryptic gene rearrangements, which cannot be detected by karyotyping, may lead to assignment of cases to incorrect prognostic classes. These problems may result in sub-optimal or over-treatment of patients. Using an artificial neural network-based analysis of HOX gene expression profiles generated by real-time quantitative PCR (RT-QPCR) we have previously shown that the favorable and intermediate cytogenetic classes are characterised by low HOXA5 (Ct value > 29.5) and high HOXB3 (Ct value < 25) expression respectively (Blood2006; 108: Abstract 2318). We have now measured HOXA5 and HOXB3 expression levels by RT-QPCR in a fresh set of 78 newly diagnosed cases of AML (31 favorable, 38 intermediate and 9 adverse karyotypes as determined by conventional cytogenetic analysis). All 31 cases with favorable cytogenetics had HOXA5 Ct values > 29.5 with twenty-nine (93.5%) having Ct values > 33. Therefore, using a HOXA5 Ct ≥; 33 to define membership of the favorable prognostic class and HOXA5 Ct < 33 to define membership of a non-favorable class, 72 cases (92.3%) were correctly assigned (29 favorable and 43 non-favorable). Of the 4 cases with non-favorable cytogenetics, originally misclassified by HOXA5 expression profiling, two were subsequently found to have cryptic rearrangements of PML-RARα and therefore should have been included within the favorable group. This increased the percentage of cases correctly assigned by HOXA5 expression profiling alone to 94.9%. We also found that within the favorable group, AML with t(15;17) or t(8;21) was characterized by low expression of HOXB3 (Ct range 30.9 to 37.4, median Ct 34.1) whereas AML with inv(16) had a distinct signature characterized by higher HOXB3 expression (Ct range 26.4 to 30.1, median Ct 28.0). In addition, we have identified a subset of patients with intermediate cytogenetics who have high white cell counts, low HOXB3 expression and an inferior response to treatment. Therefore, in AML, the measurement of expression levels of only two HOX genes, HOXA5 and HOXB3 , complements cytogenetic analysis and may improve the yield of favorable gene rearrangements detected and provide additional prognostic information for cases with intermediate or failed cytogenetics.

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