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Zhonghua Xue Ye Xue Za Zhi. 2013 Mar;34(3):247-52. doi: 10.3760/cma.j.issn.0253-2727.2013.03.015.

[The effect of the adverse events with thiopurine S-methyltransferase gene mutation on outcome of childhood acute lymphoblastic leukemia].

[Article in Chinese; Abstract available in Chinese from the publisher]

Author information

1
Depatment of Hematology, Affiliated Children's Hospital,Soochow University, Suzhou, China.

Abstract

in English, Chinese

OBJECTIVE:

To investigate thiopurine S-methyltransferase (TPMT) activity and gene promoter polymorphism to probe its significance of individual chemotherapy in acute lymphoblastic leukemia (ALL) children.

METHODS:

HPLC method was carried out to determine TPMT activity (n=100), which activity at newly diagnosed. At the same time determination of TPMT activity in healthy children (n=180), these children come from the health care clinic. Using online primer3 software design primers, PCR products were purified. To sequence TPMT gene of the patients with clinical events(n=30). According to the method to analysis of correlation between TPMT activity and toxicity.

RESULTS:

The average TPMT activities were (31.72±10.31) nmol·g⁻¹Hb·h⁻¹ and (30.70±9.67) nmol·g⁻¹Hb·h⁻¹ in ALL and healthy groups respectively, without gender differences of TPMT activities (P=0.45) in both groups. The TPMT activity with clinical events in newly diagnosed ALL patients (n=30) was (24.07±11.43) nmol·g⁻¹Hb·h⁻¹. There are significant differences of TPMT activities between severe bone marrow suppression [(20.96±7.24) nmol·g⁻¹Hb·h⁻¹] and ALL patients with clinical events groups (P<0.05). The TPMT activity of (40.46±8.18) nmol·g⁻¹Hb·h⁻¹ in recurrence children was also significantly different (P<0.05). TPMT activity in severe liver toxicity group was not significantly different (P=0. 930). Of TPMT gene sequencing in ALL patients with clinical events, only 3 children were heterozygosity mutations of TPMT*3C, while others homozygous genotype. There were significant differences of TPMT activities between heterozygosity genotype [(11.99±1.32) nmol·g⁻¹Hb·h⁻¹] and homozygous genotype groups [(24.95±11.32) nmol·g⁻¹Hb·h⁻¹] (P<0.05). There were five kinds of variations at the vicinity of the promoter region of -100 of tandem repeats (VNTR) polymorphism(*V3/*V3、*V3/*V4、*V4/*V4、*V5/*V5、*V4/*V6)without significant differences of TPMT activities among five kinds (P=0.186).

CONCLUSION:

TPMT activity was related to the gene polymorphism. TPMT activity determination had prognostic value and guided individualized treatment.

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