Background: Since December 2019, the outbreak of COVID-19 has raised a great public health concern globally. Here, we report the whole genome sequencing analysis of SARS-CoV-2 strains in Malaysia isolated from six patients diagnosed with COVID-19.Methods: The SARS-CoV-2 viral RNA extracted from clinical specimens and isolates were subjected to whole genome sequencing using NextSeq 500 platform. The sequencing data were assembled to full genome sequences using Megahit and phylogenetic tree was constructed using Mega X software.Results: Six full genome sequences of SARS-CoV-2 comprising of strains from 1st wave (25th January 2020) and 2nd wave (27th February 2020) infection were obtained. Downstream analysis demonstrated diversity among the Malaysian strains with several synonymous and non-synonymous mutations in four of the six cases, affecting the genes M, orf1ab, and S of the SARS-CoV-2 virus. The phylogenetic analysis revealed viral genome sequences of Malaysian SARS-CoV-2 strains clustered under the ancestral Type B.Conclusion: This study comprehended the SARS-CoV-2 virus evolution during its circulation in Malaysia. Continuous monitoring and analysis of the whole genome sequences of confirmed cases would be crucial to further understand the genetic evolution of the virus.
Background
Tyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukemia (CML) show a high success rate. However, a low number of patients with long-term treatment-free remission (TFR) were observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24 months, with 80% occurrence within the first 6 months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranting new biomarkers for CML.
Methods
Next Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at the molecular response in CML adult patients receiving TKIs treatment. A total of 86 samples were collected, 30 from CML patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors. NGS was conducted whereby 18 miRNAs were selected and validated by real-time RT-qPCR in triplicate.
Results
Hsa-miR-181a-5p was expressed significantly (p-value< 0.05) with 2.14 and 2.33-fold down-regulation in both patient groups, respectively meanwhile hsa-miR-182-5p and hsa-miR-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation. The down-regulation was consistent with decreased amounts of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with the substantial presence of BCR-ABL1 in CML patients treated with TKIs at the molecular response.
Conclusions
Therefore, these miRNAs have potential as new therapeutic biomarkers for BCR-ABL1 status in adult CML patients treated with TKIs at molecular responses. These could improve current approaches and require further analysis to look for targets of these miRNAs in CML.
BackgroundTyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukaemia (CML) show a high success rate. However, low number of patients with long-term treatment-free remission (TFR) is observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24 months with 80% occurrence within the first 6 months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranted new biomarkers for CML. MethodsNext Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at molecular response in CML adult patients receiving TKIs treatment. A total of 86 samples were collected, 30 from CML patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors. NGS was conducted whereby 18 miRNAs were selected and validated by real time RT-qPCR in triplicate. ResultsHsa-miR-181a-5p was expressed significantly (p-value<0.05) with 2.14 and 2.3 fold down-regulation in both patient groups respectively while hsa-miR-182-5p and hsa-miR-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation respectively. The down-regulation was consistent with decreased amount of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with substantial presence of BCR-ABL1 in CML patients treated with TKIs at molecular response. ConclusionTherefore, these miRNAs have potential as new therapeutic biomarkers for BCR-ABL1 status in adult CML patients treated with TKIs at molecular responses. These could improve current approaches and require further analysis to look for targets of these miRNAs in CML.
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