scholarly journals Methotrexate-induced subacute neurotoxicity in a child with acute lymphoblastic leukemia carrying genetic polymorphisms related to folate homeostasis

2010 ◽  
Vol 86 (1) ◽  
pp. 98-101 ◽  
Author(s):  
Jose Manuel Vagace ◽  
Cristina Caceres-Marzal ◽  
Mercedes Jimenez ◽  
Maria Soledad Casado ◽  
Silvia Gonzalez de Murillo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Folate Homeostasis ◽  
Subacute Neurotoxicity

Folate pathway genetic polymorphisms modulate methotrexate-induced toxicity in childhood acute lymphoblastic leukemia

2019 ◽  
Vol 83 (4) ◽  
pp. 755-762 ◽  
Author(s):  
Al-Motassem Yousef ◽  
Rand Farhad ◽  
Daniah Alshamaseen ◽  
Abrar Alsheikh ◽  
Mohammed Zawiah ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Folate Pathway

Pharmacogenetics of Outcome in Children with Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 163-163 ◽  
Author(s):  
Jose Claudio Rocha ◽  
Cheng Cheng ◽  
Wei Liu ◽  
Shinji Kishi ◽  
Soma Das ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphisms ◽  
Cumulative Incidence ◽  
Failure Time ◽  
Lymphoblastic Leukemia ◽  
Classification And Regression Tree ◽  
Central Nervous System Relapse ◽  
Start Site ◽  
Genetic Characteristics ◽  
Expression Levels

Abstract The acquired genetic characteristics of acute lymphoblastic leukemia (ALL) blasts are often used to guide the intensity of therapy, whereas the germline host genetic characteristics of the patient generally have not been considered. Multiple common, functionally important polymorphisms affect genes whose products determine the pharmacokinetics and pharmacodynamics of antileukemic agents. It is not yet known how genetic polymorphisms may interact to affect the outcome of antileukemic therapy. Combining classification and regression tree with failure time analysis, we assessed whether 16 genetic polymorphisms, alone or in combination, predicted relapses in 246 children with ALL, 116 of whom were treated on the lower-risk (LR) and130 on the higher-risk (HR) arms of the St Jude protocol Total XIIIB. Genotyping was performed for the following polymorphic loci: CYP3A4*1B and CYP3A5*3; GSTP1 313A>G, GSTM1 and GSTT1 deletions; MDR1 exon 21 (2677G>T/A) and MDR1 exon 26 (3435C>T); MTHFR 677C>T and MTHFR 1298A>C; NR3C1 1088A>G; SLC19A1 80G>A; TPMT 238G>C, 460G>A and 719A>G; TYMS enhancer repeat; UGT1A1 promoter repeat polymorphism; VDR intron 8 G>A and VDR FokI (start-site) T>C. In all children with available RNA in their diagnostic ALL blasts, gene expression levels of prognostic genotypes were analyzed using the Affymetrix genechip array HG_U95Av2. Among the HR group, the glutathione S-transferase M1 (GSTM1) non-null genotype was associated with the risk of hematological relapse (5-year cumulative incidence, 17.1%±4.5% compared to 5.1%±2.9% for GSTM1 null genotype, p = 0.03), and among the non-null genotypes, the thymidylate synthetase (TYMS) 3/3 genotype was associated with a further increase in hematologic relapse risk (5-year cumulative incidence, 29.2%±9.5% compared to 10.9%±4.7% for TYMS 2/3 or 2/2 genotypes, p = 0.02). Increased expression levels of these two target genes (p < 0.0001 and p = 0.09, respectively) were consistent with resistance to the drugs interacting with these gene products. For central nervous system relapse, among the HR group, the vitamin D receptor (VDR) start site (p = 0.02) and intron 8 genotypes (p = 0.04) predisposed, whereas for LR patients the TYMS 3/3 genotype predisposed (p = 0.04). The genotypes associated with outcome have pharmacologic plausibility: e.g., high GST activity (GSTM1 non-null) could cause anticancer drug resistance; high TYMS activity (TYMS 3/3) would be less inhibited by antifolates. In conclusion, germline polymorphisms influence the outcome of antileukemic therapy, and therefore represent determinants of response that can be used to optimize therapy.

scholarly journals Genetic polymorphisms of NQO1, CYP1A1 and TPMT and susceptibility to acute lymphoblastic leukemia in a Tunisian population

2012 ◽  
Vol 40 (2) ◽  
pp. 1307-1314 ◽  
Author(s):  
Slah Ouerhani ◽  
Nouha Cherif ◽  
Ikbel Bahri ◽  
Ines Safra ◽  
Samia Menif ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Tunisian Population

scholarly journals Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients

2020 ◽  
Author(s):  
Kanyarat Khaeso ◽  
Nontaya Nakkam ◽  
Patcharee Komwilaisak ◽  
Piyathida Wongmast ◽  
Su-on Chainansamit ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Dna Sequencing ◽  
Allele Frequency ◽  
Genetic Polymorphisms ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Pediatric All

AbstractGenetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of TPMT and NUDT15 were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of TPMT*3C was 0.034. Among NUDT15 variants, NUDT15*3 is the most common variant with the allele frequency of 0.073, whereas those of NUDT15*2, NUDT15*5, and NUDT15*6 variants were 0.022, 0.011, and 0.039. These data suggest that a high proportion of Thai pediatric ALL patients may be at risk of thiopurine-induced myelosuppression.

Genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemia

2004 ◽  
Vol 43 (2) ◽  
pp. 100-109 ◽  
Author(s):  
Renata Canalle ◽  
Regislaine V. Burim ◽  
Luiz G. Tone ◽  
Catarina S. Takahashi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia
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