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Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric acute lymphoblastic leukemia

Elixabet López-López1, Ángela Gutiérrez-Camino1, Maria Ángeles Piñán2

  • 1Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country (UPV/EHU), Leioa, Spain.

Plos One
|March 12, 2014
PubMed

Insights

Genetic variations in microRNAs (miRNAs) may predict treatment toxicity in pediatric acute lymphoblastic leukemia (ALL). A specific SNP in DROSHA was linked to vomiting, offering a potential new toxicity marker.

Area of Science:

  • Genetics
  • Oncology
  • Pharmacogenomics

Background:

  • Acute lymphoblastic leukemia (ALL) therapy, while successful, frequently causes toxicity.
  • Identifying genetic predictors of treatment-related adverse events is crucial for personalized medicine.
  • Previous research focused on coding regions, overlooking regulatory non-coding elements like microRNAs (miRNAs).

Purpose of the Study:

  • To identify novel toxicity markers in pediatric B-cell ALL (B-ALL) by investigating miRNA-related polymorphisms.
  • To explore how genetic variations in miRNAs affect their levels and function, potentially influencing drug response and toxicity.
  • To assess the association between miRNA single nucleotide polymorphisms (SNPs) and treatment toxicity in pediatric B-ALL patients.

Main Methods:

  • Analysis of 118 SNPs in pre-miRNAs and miRNA processing genes.
  • Study included 152 pediatric B-ALL patients treated with the LAL/SHOP protocol.
  • Statistical analysis, including False Discovery Rate (FDR) correction, was used to assess associations.

Main Results:

  • An association was detected between the SNP rs639174 in the DROSHA gene and vomiting.
  • This finding represents the first reported link between this specific miRNA-related SNP and toxicity.
  • DROSHA is known to influence miRNA expression, potentially affecting drug transport genes.

Conclusions:

  • MiRNA-related SNPs, such as rs639174 in DROSHA, show potential as predictive markers for treatment toxicity in pediatric B-ALL.
  • Further research into miRNA polymorphisms could enhance personalized treatment strategies and improve patient outcomes.
  • Genetic variations in non-coding regions offer a promising avenue for predicting and mitigating chemotherapy-induced adverse effects.

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