Acute Myeloid Leukemia
In this paper, I will be discussing the study of certain drugs and there effect on the cancer Acute Myeloid Leukemia. AML is the most common type of leukemia. Leukemia is when bone marrow makes an abnormal type of white blood cell. This is usually caused by a mutated protein of p53 and CK1a. While researching further into AML, I found what causes AML to be the most interesting. The article I am studying focuses on drug treatments for AML and the test result, using mice as the subject. Before diving into the research of this article, it is important to understand the function of CK1a and p53, and how apoptosis plays an important role in cancer.
Isoforms of the casein kinase 1 (CK1) family have been shown to phosphorylate key regulatory molecules involved in cell cycle, transcription and translation, the structure of the cytoskeleton, cell-cell adhesion and receptor-coupled signal transduction. (Schittek, Sinneburg 2018) CK1a has the main job of phosphorylating beta-catenin. When you phosphorylate beta katanin it causes it not to accumulate in the cell. The build-up of beta-catenin is one of the main causes of leukemia. This is because when beta-catenin builds up it will enter the nucleus and transcribe to the DNA molecule causing a mutation. CK1a also has the main role of keeping p53 active and stabilizing its structure.
P53 is an important protein that has the most potential when battling against cancerous cells. According to an article from Wikipedia, “The TP53 gene is the most frequently mutated gene in human cancer.” It is a cancer-suppressing protein and is used to prevent cancerous cells from spreading. The gene that makes p53 is one of the most commonly mutated genes when it comes to cancer. P53 has many important functions. It detects DNA damage and can sometimes repair DNA. If a cell is beyond repair, p53 can induce apoptosis. The authors in the article focus more on inducing apoptosis. This is one of the key factors in AML, is when p53 becomes mutated and cannot prevent the cell from
Knowing the important roles of p53 and CK1a, the researchers from this article introduced drugs to help cells complete apoptosis for cancerous cells. The article focuses on 6 CK1a inhibitors to accomplish this. Of the six, four were found to be extremely effective, I found A86 and A51 to be the most effective.
I came to this conclusion by observing tow graphs. On figure 2A, this graph clearly shows that mice treated with A86 and A51 had a 100% rate for apoptosis in cells. According to tissue surveys, the treatment relieved most of the leukemia signs from the major organs of the mice. A51 also promoted p53 synthesis based on the results of figure 2C. Not only did the researchers promote p53 gene growth, but they also improved the overall health of the mouse. This is very important for an effective treatment for human patients.
The goal of this study was not to find an exact cure for AML, but to provide a step in the right direction. There still many other contributors to AML that are not necessarily related to p53 protein or CK1a. There are various risk factors such as smoking, and genetics related to AML. I think the authors had shown real progress in treatment. I do think that this drug is ready for human treatment. Their study showed overall progression in tissue related to the major organs of the mice, and the mice lived months after being inoculated with AML. The authors of this article had a clear goal in mind to produce apoptosis and they made that goal.
References
Minzel, W., Venkatachalam, A., Fink, A., Hung, E., Brachya, G., Burstain, I., Shaham, M., Rivlin, A., Omer, I., Zinger, A., Elias, S., Winter, E., Erdman, P., Sullivan, R., Fung, L., Mercurio, F., Li, D., Vacca, J., Kaushansky, N., Shlush, L., Oren, M., Levine, R., Pikarsky, E., Snir-Alkalay, I. and Ben-Neriah, Y. (2018). Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models. Cell, 175(1), pp.171-185.e25.
Schittek, B. and Sinnberg, T. (2018). Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis.
En.wikipedia.org. (2018). P53. [online] Available at: https://en.wikipedia.org/wiki/P53 [Accessed 2 Dec. 2018].