scholarly journals Circulating miR-146a expression as a non-invasive predictive biomarker for acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samiah Shahid ◽  
Wajeehah Shahid ◽  
Jawaria Shaheen ◽  
M. Waheed Akhtar ◽  
Saima Sadaf

AbstractDysregulation of non-coding microRNAs during the course of tumor development, invasion and/or progression to the distant organs, makes them a promising candidate marker for the diagnosis of cancer and associated malignancies. This exploratory study aims at evaluating the usefulness of plasma concentration of circulating mir-146a as a non-invasive biomarker for acute lymphoblastic leukemia (ALL). Total RNA including miRNA was isolated from 110 plasma samples of patients (n = 66), healthy controls (n = 24) and follow up (n = 20) cases and reverse transcribed. Relative concentrations were assessed using real-time quantitative PCR and fold-change was calculated by 2−ΔΔCt method. Finally, relative concentrations were correlated to clinicopathological factors. Patients (n = 66) were analyzed to determine fold expression of miR-146a in plasma samples of ALL. Before chemotherapy, pediatric (n = 42) and adult (n = 24) showed overexpression of miR-146a compared with healthy controls (P < 0.0001). There was no effect of age and gender on mir-146a expression in plasma. mirR-146a expression was independent of clinical and hematological features. Moreover, miR-146a levels in plasma of paired samples (n = 20) after treatment showed significant decrease in expression (P < 0.001). Expression of plasma miR-146a may be utilized as non-invasive marker to diagnose and predict prognosis in pediatric and adult patients with ALL. Moreover predicted targets may be utilized for ALL therapy in future.

2014 ◽  
Vol 124 (2) ◽  
pp. 81-85
Author(s):  
Elżbieta Pels

Abstract Introduction. Patients with the history of neoplastic disease in childhood and adolescence, successfully treated, are at higher risk in terms of their susceptibility to develop other diseases later in their lives. Aim. The purpose of study was to evaluate saliva TNF-α concentration in the children with acute lymphoblastic leukemia with reference to gingival inflammations. Material and methods. The investigation was carried out in the group of 78 children with ALL aged 2-18yrs and analogical in terms of age and gender group of healthy controls. Results. Gingival conditions were expressed as gingival index (GI). In the group of children with ALL mean GI determined in examination 1 was 0.084±0.34, in examination 2 GI=0.007±0.04 and in examination 3 mean GI=0.017±0.13. In the group of healthy controls GI=0.003±0.03. Saliva concentration of TNF-α determined in the group of children with ALL in examination 1 ranged 4.16-135.01pg/ml. In that group in examination 1, mean saliva TNF-α concentration was 36.9±32.6pg/ml. In the group of healthy children mean saliva TNF-α concentration was 52.1±107.64pg/ml. Conclusions. The authors, who observed various increases in the concentrations of TNF-α, IL-1α, IL-6, and IL-8 in the saliva and oral tissues in the patients consider that the proinflammatory cytokines in the saliva present in significantly higher concentrations in the future may have diagnostic and predicative value as replace indices of neoplastic transformations. Monitoring of prognostic factors affecting inflammations of the oral mucosa in children with ALL is likely to prevent complications to standard treatment and prolonged time of anticancer therapy. Early evaluation of those parameters can quicken recovery and strengthen patient's health. Close cooperation between dentists and pediatricians-hematologists is important in maintaining oral health and improve the quality of life of children suffering from neoplastic diseases.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa M. Zahran ◽  
Azza Shibl ◽  
Amal Rayan ◽  
Mohamed Alaa Eldeen Hassan Mohamed ◽  
Amira M. M. Osman ◽  
...  

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.


Metabolomics ◽  
2021 ◽  
Vol 17 (7) ◽  
Author(s):  
Toshie Saito ◽  
Yue Wei ◽  
Li Wen ◽  
Chaitanya Srinivasan ◽  
Benjamin O. Wolthers ◽  
...  

2020 ◽  
Author(s):  
HUI ZHANG ◽  
Chuang Jiang ◽  
Haiyan Liu ◽  
Wenge Hao ◽  
Pengfei Wang ◽  
...  

Abstract Background Refractory/relapsed acute lymphoblastic leukemia (RR-ALL) remains to be a leading cause of treatment failure and subsequent death. Forkhead box O1 (FOXO1) belongs to the forkhead family of transcription factors, its specific role in RR-ALL has not yet been determined in B-cell ALL (B-ALL). The purpose of this study was to investigate the expression and prognostic value in ALL. Methods RNA sequencing was applied to an ALL case with induction failure to identify the causal events. The transcription activity was examined with luciferase reporter assay. FOXO1 mRNA expression level was examined using real-time quantitative PCR. Association analysis was performed to correlate FOXO1 transcription with childhood B-ALL prognosis and relapse. Results In this ALL case with induction failure, we successfully identified a novel MEIS1-FOXO1 fusion gene. The transcription activity of MEIS1-FOXO1 was significantly abolished as compared to wild-type FOXO1. Low FOXO1 expression level was strongly associate with unfavorable subtype, MRD positivity and relapse. Conclusions FOXO1 loss of function associates with ALL high-risk stratification and relapse, which might be due to drug resistance.


Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3798-3804 ◽  
Author(s):  
Tomasz Szczepański ◽  
Vincent H. J. van der Velden ◽  
Patricia G. Hoogeveen ◽  
Maaike de Bie ◽  
Daniëlle C. H. Jacobs ◽  
...  

Abstract The frequently occurring T-cell receptor delta (TCRD) deletions in precursor-B–acute lymphoblastic leukemia (precursor-B–ALL) are assumed to be mainly caused by Vδ2-Jα rearrangements. We designed a multiplex polymerase chain reaction tified clonal Vδ2-Jα rearrangements in 141 of 339 (41%) childhood and 8 of 22 (36%) adult precursor-B–ALL. A significant proportion (44%) of Vδ2-Jα rearrangements in childhood precursor-B–ALL were oligoclonal. Sequence analysis showed preferential usage of the Jα29 gene segment in 54% of rearrangements. The remaining Vδ2-Jα rearrangements used 26 other Jα segments, which included 2 additional clusters, one involv ing the most upstream Jα segments (ie, Jα48 to Jα61; 23%) and the second cluster located around the Jα9 gene segment (7%). Real-time quantitative PCR studies of normal lymphoid cells showed that Vδ2 rearrangements to upstream Jα segments occurred at low levels in the thymus (10–2 to 10–3) and were rare (generally below 10–3) in B-cell precursors and mature T cells. Vδ2-Jα29 rearrangements were virtually absent in normal lymphoid cells. The monoclonal Vδ2-Jα rearrangements in precursor-B–ALL may serve as patient-specific targets for detection of minimal residual disease, because they show high sensitivity (10–4 or less in most cases) and good stability (88% of rearrangements preserved at relapse).


2020 ◽  
Vol Volume 12 ◽  
pp. 1253-1259
Author(s):  
Sanaz Mansouri ◽  
Behzad Khansarinejad ◽  
Ghasem Mosayebi ◽  
Aziz Eghbali ◽  
Mahdieh Mondanizadeh

Leukemia ◽  
2017 ◽  
Vol 32 (4) ◽  
pp. 931-940 ◽  
Author(s):  
I S Jerchel ◽  
A Q Hoogkamer ◽  
I M Ariës ◽  
E M P Steeghs ◽  
J M Boer ◽  
...  

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