Genome-wide analysis for genomic alteration in acute promyelocytic leukaemia
Acute Promyelocytic Leukemia (APL) is a subset of acute myeloid leukemias (AML), and is commonly associated with the presence of chromosomal translocations leading to the expression of the PML-RARA fusion protein. Although chromosomal translocation has been implicated in leukemogenesis, other und...
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| Main Author: | |
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| Format: | Monograph |
| Language: | English |
| Published: |
Pusat Pengajian Sains Perubatan, Universiti Sains Malaysia
2017
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| Subjects: | |
| Online Access: | http://eprints.usm.my/57530/1/PROF%20DR%20ROSLINE%20HASSAN-Eprints.pdf http://eprints.usm.my/57530/ |
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| Institution: | Universiti Sains Malaysia |
| Language: | English |
| Summary: | Acute Promyelocytic Leukemia (APL) is a subset of acute myeloid leukemias (AML),
and is commonly associated with the presence of chromosomal translocations leading
to the expression of the PML-RARA fusion protein. Although chromosomal
translocation has been implicated in leukemogenesis, other underlying mechanisms
such as copy number variation (CNV), microRNA (miRNA) expression and gene
expression may also play important roles in the pathogenesis of APL. In this study,
we performed CNV analysis, FL T3 mutation analysis, miRNA expression profiling
and gene expression-pathway based analysis to understand the underlying mechanism
of genomic alteration involve in contributing to the different survival in subgroups of
acute promyelocytic leukaemia patients. In CNV analysis, chromosomal deletion on
subband 5q13.2, 8p23.1 and 16p 12.3 were commonly seen in six of eight cases (75%)
and gain of 2p 11.2 and 14q32.33 were found in all cases (n=8). Mutational analysis
of FLT3 genes did not show any significant finding in all patients samples. Global
miRNA profiling was performed on APL samples by using the microarray approach,
followed by Nanostring nCounter system to validate the results. MiRNA expression
profiles from nCounter platform revealed that miR-1 00 is most significantly
upregulated in APL patients as compared to normal controls. We identified most
differentially expressed genes in RAS signaling pathway, MAPK, Apoptosis and
JAK STAT signaling pathway of APL at diagnosis patients. In conclusion, this study
showed that other underlying mechanisms also play important roles In the
pathogenesis of APL. These findings provide new insights into the role of miRNAs and mRNA in the genetic origins of APL and highlight their potential as biomarkers
for disease stratification and drug-targeted therapy. |
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