Contributions
Abstract: PB1384
Type: Publication Only
Session title: Acute myeloid leukemia - Biology & Translational Research
Background
MicroRNAs (miRNAs) are small, single strands of non-coding nucleotides that are highly conserved and endogenous. MiRNAs regulate gene transcription and translation through their targeting of specific RNAs for silencing or degradation. In recent years their importance as regulators of gene expression in health and disease has been increasingly recognised, providing a new class of readily detectable biomarkers. Acute myeloid leukaemia (AML) is a rare, heterogenous and often-times difficult to treat disease. It affects children, predominantly through single genetic changes that are impactful enough to cause AML or through the accumulation of genetic change over many years in adults. However both age groups show many similarities as well as differences, the former providing new avenues for therapy.
Aims
To better understand these two forms of AML, separated by the age of onset, we have examined the miRNAs that are differentially expressed between risk subgroups in two publicly accessible databases.
Methods
We used the (1) National Cancer Institute’s Therapeutically Applicable Research to Generate Effective Treatments (NCI-TARGET) that examined paediatric patients and (2) The Cancer Genome Atlas (TCGA) that examined adults with AML to identify miRNAs that were differentually expressed between risk subgroups.
Results
Four mIRs (mIR3186, mIR486-1, mIR1915 and mIR4740) were differentially expressed (by more than two-fold levels) when comparing intermediate vs good, and poor vs good, risk subgroups in the TCGA dataset. 21 mIRs were differentially expressed in standard versus low, while only two mIRs were differentially expressed when we compared high versus low, risk subgroups, but these were expressed in both subgroup comparisons. Analysis using the TCGA-LAML dataset showed that four differentially expressed mIRs had elevated expression in the poor risk subgroups compared to intermediate and good risk TCGA subgroups. These were mir486-1 (p=2.011 x 10-12), miR378G (p=0.01594), miR1915 (p=0.01915) and miR8086 (p=0.023). In addition, below median levels of miR486-1 and miR1915 were associated with worse outcomes in adults with AML (p=0.0062 and p=0.021, respectively).
Conclusion
Future work will include pathway and ROC analysis to determine the utility of these miRs as targets for therapy and biomarkers for survival, respectively.
Keyword(s): Acute myeloid leukemia
Abstract: PB1384
Type: Publication Only
Session title: Acute myeloid leukemia - Biology & Translational Research
Background
MicroRNAs (miRNAs) are small, single strands of non-coding nucleotides that are highly conserved and endogenous. MiRNAs regulate gene transcription and translation through their targeting of specific RNAs for silencing or degradation. In recent years their importance as regulators of gene expression in health and disease has been increasingly recognised, providing a new class of readily detectable biomarkers. Acute myeloid leukaemia (AML) is a rare, heterogenous and often-times difficult to treat disease. It affects children, predominantly through single genetic changes that are impactful enough to cause AML or through the accumulation of genetic change over many years in adults. However both age groups show many similarities as well as differences, the former providing new avenues for therapy.
Aims
To better understand these two forms of AML, separated by the age of onset, we have examined the miRNAs that are differentially expressed between risk subgroups in two publicly accessible databases.
Methods
We used the (1) National Cancer Institute’s Therapeutically Applicable Research to Generate Effective Treatments (NCI-TARGET) that examined paediatric patients and (2) The Cancer Genome Atlas (TCGA) that examined adults with AML to identify miRNAs that were differentually expressed between risk subgroups.
Results
Four mIRs (mIR3186, mIR486-1, mIR1915 and mIR4740) were differentially expressed (by more than two-fold levels) when comparing intermediate vs good, and poor vs good, risk subgroups in the TCGA dataset. 21 mIRs were differentially expressed in standard versus low, while only two mIRs were differentially expressed when we compared high versus low, risk subgroups, but these were expressed in both subgroup comparisons. Analysis using the TCGA-LAML dataset showed that four differentially expressed mIRs had elevated expression in the poor risk subgroups compared to intermediate and good risk TCGA subgroups. These were mir486-1 (p=2.011 x 10-12), miR378G (p=0.01594), miR1915 (p=0.01915) and miR8086 (p=0.023). In addition, below median levels of miR486-1 and miR1915 were associated with worse outcomes in adults with AML (p=0.0062 and p=0.021, respectively).
Conclusion
Future work will include pathway and ROC analysis to determine the utility of these miRs as targets for therapy and biomarkers for survival, respectively.
Keyword(s): Acute myeloid leukemia