29 Jan Genetic Basis For Acute Lymphoblastic Leukemia Drug Toxicity Identified

MedicalResearch.com Interview with:
Jun J. Yang  Ph.D.
Assistant Member Dept. of Pharm. Sci.
St. Jude Children’s Research Hospital
Memphis, TN 38105

Medical Research: What is the background for this study? What are the main findings?

Dr. Yang: Mercaptopurine is highly effective in acute lymphoblastic leukemia (ALL) and essential for the cure of this aggressive cancer. However, it also has a narrow therapeutic index with common toxicities. Identifying genetic risk factors for mercaptopurine toxicity will help us better understand how this drug works and also potentially enable clinicians to individualize therapy based on patients’ genetic make-up (precision medicine).

In addition to confirming the role of TPMT, we have identified another important genetic risk factor (a genetic variation in a gene called NUDT15) for mercaptopurine intolerance. Patients carrying the variant version of NUDT15 are exquisitely sensitive and required up to 90% reduction of the normal dose of this drug. TPMT variants are more common in individuals of African and European ancestry, whereas NUDT15 variants are important in East Asians and Hispanics.

Medical Research: What should clinicians and patients take away from your report?

Dr. Yang: There is clearly a genetic basis for mercaptopurine toxicity. For example, patients carrying variant versions of TPMT and NUDT15 are at much higher risk of experiencing excessive toxicities from mercaptopurine therapy.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Yang: The  genetic basis of mercaptopurine response (or response to any drugs) is complex involving many genes. Continued research in this area (pharmacogenomics) is likely to reveal critical knowledge with potential clinical relevance. Also, racial and ethnic diversity is an important consideration for future research of pharmacogenomics on a global scale.

Citation:

J Clin Oncol. 2015 Jan 26. pii: JCO.2014.59.4671. [Epub ahead of print]

Inherited NUDT15 Variant Is a Genetic Determinant of Mercaptopurine Intolerance in Children With Acute Lymphoblastic Leukemia.

Yang JJ¹, Landier W², Yang W², Liu C², Hageman L², Cheng C², Pei D², Chen Y², Crews KR², Kornegay N², Wong FL², Evans WE², Pui CH², Bhatia S², Relling MV².

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MedicalResearch.com Interview with Jun J. Yang Ph.D. (2015). Genetic Basis For Acute Lymphoblastic Leukemia Drug Toxicity Identified MedicalResearch.com

Last Updated on January 29, 2015 by Marie Benz MD FAAD