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The relationship between thiopurine methyltransferase activity and genotype in blasts from patients with acute leukemia

Lookup NU author(s): Dr Sally Coulthard, Dr Christopher Howell, Jill Robson, Emeritus Professor Andy Hall

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Abstract

The level of expression of the enzyme thiopurine methyltransferase (TPMT) is an important determinant of the metabolism of thiopurines used in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), Studies in red blood cells (RBC) have shown that TPMT expression displays genetic polymorphism with 11% of individuals having intermediate and one in 300 undetectable levels. The genetic basis for this polymorphism has now been elucidated and polymerase chain reaction (PCR)-based assays described for the most common mutations accounting for reduced activity. In previous studies, genotype has been correlated with red blood cell activity. In this report, we describe the relationship between genotype and TPMT activity measured directly in the target of drug action, the leukemic cell. We have demonstrated that the TPMT activity in lymphoblasts from 38 children and adults found by PCR to be homozygotes (*1/*1) was significantly higher than that in the five heterozygotes (*1/*3) detected (median, 0.25 v 0.08, P < .002, Mann-Whitney U), Similar results were obtained when results from children were analyzed separately, However, comparison of activity in blasts from AML and ALL showed a higher level in the former (0.35 v 0.22 nU/mg, P < .002, n = 17, 35), suggesting that facto rs other than genotype may also influence expression. (C) 1998 by The American Society of Hematology.


Publication metadata

Author(s): Coulthard SA, Howell CI, Robson J, Hall AG

Publication type: Article

Publication status: Published

Journal: Blood

Year: 1998

Volume: 92

Issue: 8

Pages: 2856-2862

Print publication date: 01/10/1998

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

URL: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/92/8/2856

PubMed id: 9763570


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