Abstract 3809
Background
Dysregulation of various miRNAs has been linked to the initiation and progression of several cancers including acute myeloid leukemia (AML). However, their role in pediatric cytogenetically normal AML (CN-AML) is still unclear. The objective of the present study was to identify deregulated miRNA expression patterns and their correlation with survival outcome in pediatric CN-AML.
Methods
The study was approved by Institutional Ethical Committee. Informed written consent was taken from all the subjects. Bone marrow (BM) samples from 36 pediatric CN-AML patients and 20 pediatric controls (with solid tumors without BM involvement) were collected and used for isolation of mononuclear cells, genomic DNA and total RNA. Various clinical parameters were accessed and mutation status (NPM1 and FLT3-ITD) determined by PCR. Total RNA from 10 samples (5 CN-AML and 5 controls) was used for global miRNA profiling on Illumina HiSeq2500 platform and data were analysed using bioinformatic pipeline. For all 36 CN-AML patients, cDNA was prepared using TaqMan advanced miRNA cDNA synthesis kit followed by qPCR using TaqMan advanced miRNA assay for selected miRNAs.
Results
Global miRNA profiling revealed differential expression of 168 miRNAs of which 66 were upregulated and 102 were downregulated (fold change>1.5, p ≤ 0.05) in pediatric CN-AML patients. Interestingly, 40 miRNAs belonging to human 14q32 miRNA cluster were significantly downregulated in CN-AML patients. The expression of 11 miRNAs selected for qPCR-based validation based on their involvement in signalling pathways in AML (and other cancers), were found to be dysregulated in 36 patients. Most of these miRNAs were found to target genes involved in the initiation and progression of AML. Importantly, there was a significant correlation between expression levels of miR-75, miR-589, miR-4446, miR-889, and miR-654 and survival outcomes like Event-free, Disease-free, and Overall survival. Clinical parameters like TLC, ANC, LDH, Blast percentage were also significantly correlated with survival outcomes.
Conclusions
Along with various genetic abnormalities, deregulation in the expression of miRNAs might be an important contributor to the development of pediatric CN-AML.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Department of Biotechnology, Government of India.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract