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
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract
3140 - Phase 2 study of olaparib in previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) or homologous recombination repair deficiency (HRD): LYNK-002
Presenter: David Hyman
Session: Poster Display session 3
Resources:
Abstract