Causes and Development of Chronic Myeloid Leukemia
Chronic Myeloid Leukemia (CML) is a type of blood cancer that advances when there is an abnormally large amount of white blood cell production (Cancer council, Online). The occurrence CML develops from a DNA from stem cell through damaged bone marrow. The damage cells mutate to leukemia cell and multiply into chronic myeloid leukemia. It grows and survives better than the normal cells. It does not interfere with the mature development of red cells, white cells and platelets. This leads to lower number of normal cells in the body. From a study in 2018, 1 in 100,000 people were affected by this cancerous disease (Jabbour & Kantarjian, 2020).
The occurrence of Philadelphia chromosome occurrence and the fusion of BCR-ABL1 gene have been associated with CML. All the cases of CML are caused by the fusion of BCR-ABL1 gene. This gene occurs due to translocation process. The gene is formed through translocation process between the 9 and 22 chromosomes in the bone marrow during the cell division process. The abnormal chromosome 22 is referred to the as the Philadelphia chromosome. Studies have shown that more than 95% of CML have this chromosome. Genes are crucial instructional assets in the protein development. The BCR-ABL1 oncogen is associated with abnormal protein referred to as the BCR-ABL1 tyrosine kinase which is linked to the development of CML cells.
Current evidence have shown that the progression of leukemia is dramatic to the host immune system and leukemia cells (Curran, Godfrey & Kline, 2017). The malignant cell tends to escape the surveillance through the cell secreted factors which are crucial in attenuating host immune attacks (Boyiadzis, & Whiteside, 2017).
The overall testing of CML allows for the detection of the philadelphia chromosome and BCR-ABL1 transcripts or gene which makes the RNA copies of the abnormal DNA stretches. The presence of this abnormal gene hence confirms the clinical presentation of the CML.
There are varied methods of detecting the BCR-ABL1; cytogenetics allows for detection of numerical and structural abnormalities, fluorescence in situ hybridization uses fluorescent dye to light p the sequence if present, final method is polymerase chain reaction whereby it uses quantitative and qualitative approaches in detecting the RNA transcripts of BCR-ABL1. Occurrence of secondary mutations can be detected through DNA sequencing approaches.
Cluster differentiation (CD) is a protocol methid essential for investigating cell surface molecules. It is a member of tetraspanin family. Tetraspanin or CD cluster of Differentiation (CD) molecules are involved in processes such as cellular activation, adhesion differentiation and tumor invasion. Changes in the expression of CD63 gene is related to malignancy in cells and could be used as biomarkers for detection in neoplastic conditions. CD63 has been associated with tumour progression processes which can be vital in this case in detecting RNA transcripts of BCR-ABL1. CD63 antigen encodes the CD63 gene and is mainly associated in the intracellular vesicles.
In this experiment, cells from a 53-year-old chronic myelogenous leukemia patient were used to examine the pattern and level of CD63 gene in response to cell differentiation. CD molecules could be used as biomarkers for measuring the severity of the disease and to what level it has metastasized
Symptoms of Chronic Myeloid Leukemia
Isolation of RNA was carried out, followed with measuring the optical density of 1 micro/liter of the RNA sample using a spectrophotometer, called NanoDrop, to establish purity of RNA. Reverse transcription of RNA to cDNA along with quantification PCR were carried out.
The results demonstrated that treatment with PMA to induce immune response and caused cell-differentiation. The primer dimmers produced a melt curve with our gene of interests melting at 72oC. Electrophoresis showed two distinct bands demonstrating good quality RNA. The ratio displayed at 2:1 depicting pure RNA. CD63 cycle decreased as the number of copies increased. The CD63 response to PMA activated induction CL cell culture line.
K562 cells are differentiated into bcr:abl fusion gene expression. They bear proteomic resemblance. In cultures, they tend to exhibit less clumping ability as compared to other lines especially due to the down regulation of the surface adhesion molecules linked to bcr:abl (5). Another study by Kariamini et al (2014) has demonstrated that over expression of the cells is increased through cell adherence to the cell culture. K562 cells have been show to develop key features such as those of granulocytes, monocytes and erythrocytes and can be kill with natural killer cells due to limited MHC complex necessary for inhibiting NK activity (Jabbour & Kantarjian, 2020). Furthur to Philadelphia chromosome exhibit the reciprocal translocation process in the chromosome 15 and 17.
Many factors play a key role in the cell cycles of the k562 cells. These are not limited to the growth process, differentiation process and apoptosis (Curran, Godfrey & Kline, 2017). The leukemia cells growth are managed by the cell differentiation or occurrence of apoptosis (Raposo & Stoorvogel 2013). The occurring cell differentiation process can be induced by the undifferentiated progenitor checks which causes alteration to the morphology and phenotype of the k562 cells. These changes in the phenotypes lead to terminal paths of k562 cells to mature eryhroids, monocytes and mature macrophages. These changes can lead to increased cells sensitivity to drugs leading to apoptosis occurrence.
The overabundances of the Auroara kinases can play a critical role in the spindle formation and separation of chromosomes (Paulaitis, Agarwal & Nana-Sinkam, 2018). These functions are essential in dividing and generating the tissues and play key roles in homeostatic functions. The abundances of aurora allows for faster cellular division which in most cases are cancerous. Inhibition of these processes is critical so as to prevent the cells from mitosis progression (Paulaitis, Agarwal & Nana-Sinkam, 2018).
The over expression demonstrated by this study shows that there are molecular events which enable the tumors to evade the apoptotic death. Exosomes present have been found to be critical in influencing the underlying pathways. A key example is the transforming growth factor β1 (TGF- β1) which regulates the differentiation process, apoptosis and cancer cell type migration (Ikushima & Miyazono, 2010). Studies have shown that the activation of the TGF-β1 activates PI3K/Akt/NF-kB/MMP9 pathways are present in philadelphia chromosome process (Wu et al., 2017). This can thus illustrate the long cell expression as evidnced by the usage of the PMA immune stimulation process. The difference in the expression as compared to the GAPDH gene is similar (Jørgensen et al., 2005).
In varied cell types such as the fibroblasts and T lymphocytes, PMSA has been show to stimulate the cell proliferation process demonstrating a role of the protein kinase C. further on this activity levels the effect on the activation of the terminal differentiation has been demonstrated by this study similarly to other studies undertaken (Milkovi? et al., 2019). Occurrence of the macrophage differentiation and them to gene-activated protein kinase tends to be activated during the HL60 cells differentiation process (Maybruck et al., 2017). In this study the activity of mutagen-activated protein kinase was shown to increased with PMA dose dependency expressing the tumour cells in CML occurrence.
It is essential to presume that the K562 cells exosomes tend to accelerate the tumour proliferation process through the CD63 gene expression over time. The PMA mimics the natural stimulation response. The CML exosomes thus need comproehsive in vivo and invitro studies to enable study the differentiation process of monocytic and megaryotic k562 cells.
References
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Chronic Myeloid Leukemia. Accessed at https://www.cancercouncil.com.au/chronic-myeloid-leukaemia/ on 01/04/2022.
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Jabbour, E., & Kantarjian, H. (2020). Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. American journal of hematology, 95(6), 691-709.
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