Gene expression profiling on CML patients with Philadelphia translocation.

OBJECTIVE: The use of tyrosine kinase inhibitors (TKIs) and other targeted therapeutics plays a pivotal role in treatment management for individuals diagnosed with chronic myeloid leukemia (CML). However, some patients may experience fewer favorable outcomes and treatment resistance. Our work aims to use whole transcriptome sequencing to evaluate the variations in gene expression patterns among individuals with CML based on their response to TKI therapy. PATIENTS AND METHODS: Ten blood samples were obtained from two groups of patients diagnosed with CML: those at the initial diagnosis stage and those at the recurrence stage. RNA extraction was performed on all samples and used for next-generation sequencing. The data analysis was performed using the DESeq2 R program. RESULTS: In total, 499 genes were identified as having statistically significant differences in expression levels between the two groups. Of these, 122 genes exhibited upregulation, and 377 genes exhibited downregulation. We observed a notable dysregulation in the expression levels of NTRK2 (with a fold change more significant than +5). A significant proportion of the genes that were expressed demonstrated involvement in several biological processes, including the cell cycle, PI3K-AKT signaling system, cellular senescence, oxidative phosphorylation, microRNA in cancer, FOXO signaling pathway, P53 signaling pathway, and other related pathways. CONCLUSIONS: The results demonstrate a correlation between signaling pathways and the development of treatment resistance in patients with CML. These pathways exhibited enhanced efficacy in transmitting signals downstream of the TKI target, BCR-ABL. Several target genes require additional validation in a more extensive cohort study to verify their correlation with TKI resistance. The present research highlights that many BCR-ABL-independent pathways may be correlated with resistance, thus enhancing the prospective therapy options for patients with CML.

The correlation between copy number variation in Chromosome 14 and DNA methylation in Saudi autistic children.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that represents a range of aberrant behaviour symptoms such as repetitive behaviours and defects in social communication. The prevalence of ASD has been increasing worldwide and many studies have reported that both genetic and epigenetic factors play an important role in the etiology of this disorder. The aim of this study was to investigate the implementation of DNA methylation and Copy number variation (CNV) in the diagnosis of ASD. PATIENTS AND METHODS: This study was carried out on 14 Saudi autistic children and four of their healthy siblings. Comparative genomic hybridization array was used to identify CNV in chromosome 14 and MethyLight qPCR was used to estimate levels of DNA methylation. RESULTS: The results identified CNVs in six cytobands in chromosome 14 for 13 out of 14 autistic samples: 14q11.1-q11.2, 14q11.2, 14q12, 14q21.1, 14q32.2, and 14q32.33. However, some of these cytobands were also found in normal samples with different sizes. Interestingly, chromosomal abnormalities in 14q11.1-q11.2 was only found in ASD samples. The result also showed an increase in methylation ratio of ASD samples in those CNV regions compared with their siblings. CONCLUSIONS: The findings suggest that CNV in 14q11.1-q11.2 might be a potential target in ASD diagnosis and further work is required to detect which biological pathways are affected.