Genetic polymorphism of γ-glutamyl hydrolase in Chinese acute leukemia children and identification of a novel double nonsynonymous mutation

Pediatric Hematology and Oncology
Xiao-wen ChenChanggang Li

Abstract

γ-Glutamyl hydrolase (GGH) plays a central role in folate metabolism and antifolate action. Polymorphism in the human GGH gene (GGH) was associated with efficacy and side effects of methotrexate for treatment of acute lymphoblastic leukemia (ALL). This study aimed to identify polymorphisms of GGH in Chinese. Seventy-one children with ALL, 25 children with acute myeloid leukemia (AML), and 132 children with nonmalignancy as control were included. Human GGH cDNAs were prepared and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR)-denaturing gradient gel electrophoresis. The detected variants were further confirmed by DNA sequencing. Novel variant GGH cDNA was cloned, expressed, and characterized. Allelic frequency of GGH 452C→T polymorphism was determined as 9.2% (CT, 11/71; TT, 1/71) in the ALL group, 8.0% (CT, 4/25; TT, 0/25) in the AML group, and 9.1% (TT, 4/132; T/C, 16/132) in the controls, respectively. The total allelic frequency in the Chinese population (9.0%) was higher than those reported in Japanese (5.6%) and African Americans (4.4%), and was similar to Caucasians (10.0%). Association of 452TT+TC with increased rate of hepatotoxicity and mucositis was observed in the ALL patients. Two novel mutatio...Continue Reading

References

Mar 1, 1985·The Journal of Clinical Investigation·S KoizumiB A Chabner
Mar 31, 2000·Pharmacology & Therapeutics·J GalivanD Yin
Jun 24, 2006·The Oncologist·Brigitte C Widemann, Peter C Adamson
Apr 6, 2007·Biological & Pharmaceutical Bulletin·Hideki HayashiKunihiko Itoh
Jun 29, 2010·Pediatric Blood & Cancer·Xiaowen ChenChanggang Li

❮ Previous
Next ❯

Citations

May 30, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yang Chen, Zuojun Shen
Dec 28, 2018·The Journal of Experimental Medicine·Yuxiang Zheng, Lewis C Cantley
Sep 22, 2018·The Pharmacogenomics Journal·Andrea Giletti, Patricia Esperon
Dec 25, 2019·Pediatric Hematology and Oncology·Rizal Husaini RazaliMohd Zaki Salleh
Apr 2, 2021·Critical Reviews in Oncology/hematology·Hedy MaagdenbergBruce C Carleton

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.