Leukemia and Pharmacogenetics

M8 Case Study – Pharmacogenetics This case study delves deeper into personalized medicine, by presenting a scenario based on a wide range of individual responses to the drug used to treat acute lymphocytic leukemia. You will interpret data similar to those initially published in scientific journals in order to learn more about pharmacogenomics and make recommendations about the appropriate medical treatment based on an individual’s genotype. Click on the following link to view a case study about pharmacogenetics: Case Study – Pharmacogenetics: Using Genetics to Treat Disease https://sciencecases.lib.buffalo.edu/files/pharmacogenetics.pdf Download the Case Study Report Form, fill in the answers, and submit. M8 Case Study Report Form For assistance with issues such as library resources, citing sources, plagiarism, tutoring, writing assistance, etc., browse the links that appear when you click on the tabs across the top banner of the course page to find further information.M8 Case Study Report FormStudy the case study about leukemia and pharmacogenetics:Pharmacogenetics: Using Genetics to Treat DiseaseAdd your answers to the following questions from the case study and then submit this completed case study report form.Part I – Acute Lymphocytic (Lymphoblastic) Leukemia1a. Suggest a reason why the drug might affect the two girls differently.1b. What tests might Dr. Ryder order to determine why the two girls are reacting as they are to the drug? Provide two or three appropriate examples of tests.Part II – Enzyme Activity2a. If Dr. Ryder had 10 Caucasian patients in the next month, how many would you predict to have each of the TPMT enzyme activity levels, based on the graph above?Low:Medium:High:2b. Would you expect the actual/observed number of patients to be different? Why might there be differences?2c. Which bar (low, medium, or high) represents individuals who might be homozygous for a “low enzyme activity’” version of the gene? Which bar represents individuals who might be homozygous for a “high enzyme activity” version of the gene? Which bar represents heterozygotes?2d. Answer the question: “How does enzyme activity level vary among the patients examined?” In your answer, be sure to include supporting data from the graph above. Explain how these data support your conclusion.2e. Challenge question: The actual graph (below) showed much more detail. Why do you think that there is more variation between patients than shown in the simplified graph?Part III – TPMT Enzyme Activity Levels3a. Why would individuals with the lowest level of enzyme get the sickest when they take the drug? Suggest one possible reason.3b. Describe the relationship between TPMT enzyme activity levels and TGN levels. Be sure to include supporting data from the graph.Part IV – Putting It All Together4. In the paragraphs below, indicate the correct answers (high or low, heterozygous or homozygous) with a different color or by underlining:From her research, Dr. Ryder hypothesized that patients such as Laura (who became very sick upon receiving the drug) have very high / low TPMT enzyme activity and therefore very high / low levels of TGN nucleotides at normal doses. They easily became sick from the effects of the drug, and could even die. These patients are homozygous / heterozygous for the version of the gene encoding high / low enzyme activity. A better drug dose for these patients is 1/10th the level of other patients.Patients such as Beth with high / low TPMT enzyme activity had high / low levels of TGN nucleotides. These patients would do well with the drug, and in some cases might even need a larger-than-normal dosage for the treatment to be most effective. These patients were either homozygous for the version of the gene encoding high / low enzyme activity, or were heterozygous.Based on the graph in Part II, about 10% of the Caucasian population is homozygous / heterozygous.Part V – SNPs and TPMT5a. Dr. Ryder now has the ability to conduct a SNP genetic test on her patients to determine what level of drug they should get. A new patient on the ward, Kevin, is homozygous for TPMT3A*. The graph shown in Part III is reproduced on the next page. Circle (describe) the area of the graph that might likely corresponds to Kevin’s TGN and enzyme activity levels. Explain why you circled that region.5b. What level of the drug (low, medium, or high) should Dr. Ryder give him? Explain your answer.5c. In your own words, summarize how knowing someone’s TPMT DNA sequence could be used to determine what kind of medical care they should receive.

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