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RG, a 6-year-old child, has been diagnosed with Acute Lymphoblastic Leukemia (ALL). The standard treatment is 6-mercaptopurine (Purinethol), an inexpensive drug that inhibits proliferation and is effective against rapidly proliferating cells like cancer cells. The compound is an antimetabolite that interferes with DNA synthesis. However, about 10% of patients experience life-threatening toxicities. 6-mercaptopurine is metabolized and detoxified by the enzyme thiopurine-S-methyltransferase (TPMT). The most common SNPS correlated with low enzymatic activity are TPMT*3A, *3B, *3C and *2. They cause enhanced degradation of the enzyme. Genotyping reveals that RG has the following genotype: TPMT*3A/*2. Questions: 1. A patient with low TPMT enzyme activity would: Accumulate 6-mercaptopurine and experience toxic side effects Metabolize 6-mercaptopurine quickly and experience no anti-cancer benefits 2. The gene encoding TPMT has been sequenced in RG: TPMT*3A/*2. The patient would be classified as: poor metabolizer normal/extensive metabolizer rapid metabolizer 3. Given the TPMT*3A/*2 genotype, what dose adjustment would you recommend? Reduced dose Normal dose Increased dose

RG, a 6-year-old child, has been diagnosed with Acute Lymphoblastic Leukemia (ALL). The standard treatment is 6-mercaptopurine (Purinethol), an inexpensive drug that inhibits proliferation and is effective against rapidly proliferating cells like cancer cells. The compound is an antimetabolite that interferes with DNA synthesis. However, about 10% of patients experience life-threatening toxicities. 6-mercaptopurine is metabolized and detoxified by the enzyme thiopurine-S-methyltransferase (TPMT). The most common SNPS correlated with low enzymatic activity are TPMT*3A, *3B, *3C and *2. They cause enhanced degradation of the enzyme. Genotyping reveals that RG has the following genotype: TPMT*3A/*2. Questions: 1. A patient with low TPMT enzyme activity would: Accumulate 6-mercaptopurine and experience toxic side effects Metabolize 6-mercaptopurine quickly and experience no anti-cancer benefits 2. The gene encoding TPMT has been sequenced in RG: TPMT*3A/*2. The patient would be classified as: poor metabolizer normal/extensive metabolizer rapid metabolizer 3. Given the TPMT*3A/*2 genotype, what dose adjustment would you recommend? Reduced dose Normal dose Increased dose

Biochemistry
Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
Section: Chapter Questions
Problem 1P
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RG, a 6-year-old child, has been diagnosed with Acute Lymphoblastic Leukemia (ALL). The standard treatment is 6-mercaptopurine (Purinethol), an inexpensive drug that inhibits proliferation and is effective against rapidly proliferating cells like cancer cells. The compound is an antimetabolite that interferes with DNA synthesis. However, about 10% of patients experience life-threatening toxicities. 6-mercaptopurine is metabolized and detoxified by the enzyme thiopurine-S-methyltransferase (TPMT). The most common SNPS correlated with low enzymatic activity are TPMT*3A, *3B, *3C and *2. They cause enhanced degradation of the enzyme. Genotyping reveals that RG has the following genotype: TPMT*3A/*2. Questions: 1. A patient with low TPMT enzyme activity would: Accumulate 6-mercaptopurine and experience toxic side effects Metabolize 6-mercaptopurine quickly and experience no anti-cancer benefits 2. The gene encoding TPMT has been sequenced in RG: TPMT*3A/*2. The patient would be classified as: poor metabolizer normal/extensive metabolizer rapid metabolizer 3. Given the TPMT*3A/*2 genotype, what dose adjustment would you recommend? Reduced dose Normal dose Increased dose 4. A patient with TPMT*1/*1 should receive what kind of dose? Reduced dose Standard dose Increased dose
Transcribed Image Text:RG, a 6-year-old child, has been diagnosed with Acute Lymphoblastic Leukemia (ALL). The standard treatment is 6-mercaptopurine (Purinethol), an inexpensive drug that inhibits proliferation and is effective against rapidly proliferating cells like cancer cells. The compound is an antimetabolite that interferes with DNA synthesis. However, about 10% of patients experience life-threatening toxicities. 6-mercaptopurine is metabolized and detoxified by the enzyme thiopurine-S-methyltransferase (TPMT). The most common SNPS correlated with low enzymatic activity are TPMT*3A, *3B, *3C and *2. They cause enhanced degradation of the enzyme. Genotyping reveals that RG has the following genotype: TPMT*3A/*2. Questions: 1. A patient with low TPMT enzyme activity would: Accumulate 6-mercaptopurine and experience toxic side effects Metabolize 6-mercaptopurine quickly and experience no anti-cancer benefits 2. The gene encoding TPMT has been sequenced in RG: TPMT*3A/*2. The patient would be classified as: poor metabolizer normal/extensive metabolizer rapid metabolizer 3. Given the TPMT*3A/*2 genotype, what dose adjustment would you recommend? Reduced dose Normal dose Increased dose 4. A patient with TPMT*1/*1 should receive what kind of dose? Reduced dose Standard dose Increased dose
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