scholarly journals Association between TLR2 and TLR4 Expression and Response to Induction Therapy in Acute Myeloid Leukemia Patients

2018 ◽  
Author(s):  
Mani Ramzi ◽  
Abolfazl Khalafi-Nezhad ◽  
Mahdiyar Iravani Saadi ◽  
Zahra Jowkar
Keyword(s):  
Acute Myeloid Leukemia ◽  
Mrna Expression ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Laboratory Data ◽  
Tlr4 Expression ◽  
Expression Levels ◽  
The Mean ◽  
Acute Myeloid

Background: Toll-like receptors (TLRs) are a family of transmembrane pattern-recognition receptors that play a crucial role in the realization of innate and adaptive immune response. TLRs may play a role in tumor development and growth because of expression or up-regulation of functional TLRs in some tumors and tumor cell lines. The participation of TLRs in the pathogenesis of acute myeloid leukemia (AML) remains unspecified. This study aimed to investigate the effect of TLR2 and TLR4 expression in peripheral blood mononuclear cells of AML patients in response to induction chemotherapy. Materials and Methods: Eighty- five patients with newly diagnosed AML were evaluated. Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2 and TLR4 was measured before starting and after induction chemotherapy. The differences in the mean expression levels of TLR2 and TLR4 before and after chemotherapy were compared using a paired t-test. The mean expression levels of TLR2 and TLR4 regarding laboratory data were analyzed by one-way ANOVA and Chi-square test. Results: We found that the mRNA expression of TLR2 after induction chemotherapy was significantly lower as compared to before treatment (p=0.001). Also, we found a lower TLR4 gene expression level after chemotherapy as compared to before chemotherapy, albeit it was not statistically significant (p=0.21). Moreover, we observed significantly higher expression of TLR2 and TLR4 in AML-M3 cases compared to non-M3 AML patients. Conclusion: The decreased expression of TLR4 in leukemic samples after induction chemotherapy might indicate a novel potential prognostic role for this receptor, particularly in AML-M3 cases.

scholarly journals FOXC1 Expression in Acute Myeloid Leukemia: Potential Predictor of Disease Relapse and/or Refractory Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5260-5260 ◽  
Author(s):  
Mahesh Swaminathan ◽  
Tor W Jensen ◽  
Tania Ray ◽  
Neal D Andruska ◽  
Anit Shah ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Confidence Interval ◽  
Mrna Expression ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Hazard Ratio ◽  
Disease Relapse ◽  
Potential Predictor ◽  
Equity Ownership ◽  
Acute Myeloid

Abstract Background: The mesenchymal transcription factor Forkhead Box C1 (FOXC1), derepressed in hematopoietic stem progenitor cells (HSPCs) in the setting of acute myeloid leukemia (AML), but not in normal HSPCs, was recently demonstrated to play an important role in AML disease onset and progression by blocking myeloid lineage differentiation and enhancing clonogenic potential. Herein we sought to further examine the prognostic value of FOXC1 in AML and whether FOXC1 expression is a potential predictor of disease relapse and/or lack of response to induction chemotherapy in AML. Methods: Expression of FOXC1 mRNA in mixed karyotype AML bone marrow samples was examined using publicly available microarray datasets (n=521, n=244). The clinical significance of FOXC1 gene expression as a prognostic biomarker was evaluated using censored overall survival (OS) and event-free survival (EFS) data. Degree of statistical significance in the univariate and multivariate analyses performed was assessed using log-rank test and Cox regression model, respectively. Results: FOXC1 mRNA expression was a significant predictor of OS on univariate (hazard ratio [HR] 1.592 95% confidence interval [CI] 1.263-2.007, P = 0.0001) and multivariate (HR 1.755 95% CI 1.355-2.273, P < 0.0001) analyses. This effect on OS could be attributed to disease relapse and/or lack of response to induction chemotherapy as FOXC1 mRNA expression also proved to be a significant predictor of EFS on univariate analysis (hazard ratio [HR] 1.539 95% confidence interval [CI] 1.208-1.961, P = 0.0002) and multivariate analysis (HR 1.678 95% CI 1.280-2.201, P = 0.0001), independent of age, FLT3 ITD status, NPM1 status or cytogenetic risk status. Compared to patients who experienced disease remission, FOXC1 expression was significantly elevated in patients experiencing disease relapse following induction chemotherapy (P<0.02), and in patients who were non-responders to induction chemotherapy (P<0.002) Conclusions: FOXC1 expression in AML is an independent prognostic predictor of decreased OS and EFS and is significantly associated with disease relapse and/or refractoriness to induction chemotherapy. A risk of relapse/non-response score that incorporates FOXC1 expression status may prove to be of value in identifying patients at the time of initial diagnosis who are likely to fail induction chemotherapy. Further studies are warranted to explore the prognostic and predictive utility of FOXC1 expression in the clinical management of AML. Figure Figure. Disclosures Ray: Onconostic Technologies, Inc.: Employment. Shah:Onconostic Technologies, Inc.: Employment. Ray:Onconostic Technologies, Inc.: Consultancy, Equity Ownership; 3N Diagnostics Ltd.: Consultancy, Equity Ownership.

scholarly journals The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings

2021 ◽  
Vol 8 ◽  
pp. 204993612110365
Author(s):  
Kundan Mishra ◽  
Suman Kumar ◽  
Sandeep Ninawe ◽  
Rajat Bahl ◽  
Ashok Meshram ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Febrile Neutropenia ◽  
Burkholderia Cepacia ◽  
Myeloid Leukemia ◽  
Tertiary Care ◽  
Care Hospital ◽  
Significant Difference ◽  
The Mean ◽  
Acute Myeloid

Introduction: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30–66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML. Method: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included. Result: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12–71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days ( p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 ( p = 0.063). Thirteen patients (23.63%) died during the study period. Discussion: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections. Conclusion: Infections continues to be a major cause of morbidity and mortality among 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 The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

2021 ◽  
Vol 10 ◽  
pp. e2288
Author(s):  
Mahdiyar Iravani Saadi ◽  
Mani Ramzi ◽  
Aliasghar Karimi ◽  
Maryam Owjfard ◽  
Mahmoud Torkamani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Quantitative Polymerase Chain Reaction ◽  
Remission Induction ◽  
Response To Chemotherapy ◽  
Before And After ◽  
Acute Myeloid

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

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