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New Haplotypes of the ATP Synthase Subunit 6 Gene of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia in Saudi Arabia

  • Yacoub, Haitham Ahmed (Cell Biology Department, Genetic Engineering and Biotechnology Division, National Research Center) ;
  • Mahmoud, Wael Mahmoud (Human Cytogenetics, Human Genetics & Genome Research Division, National Research Center) ;
  • El-Baz, Hatim Alaa-Eldeen El-Din (Clinical Biochemistry Department, Faculty of Medicine - North Jeddah Branch, King Abdulaziz University) ;
  • Eid, Ola Mohamed (Human Cytogenetics, Human Genetics & Genome Research Division, National Research Center) ;
  • El-Fayoumi, Refaat Ibrahim (Medical Laboratories Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University) ;
  • Mahmoud, Maged Mostafa (King Fahd Medical Research Center, King Abdulaziz University) ;
  • Harakeh, Steve (Special Infectious Agents Unit, Jeddah, Kingdom of Saudi Arabia) ;
  • Abuzinadah, Osama H.A. (Biological Sciences Department, Faculty of Sciences, King Abdulaziz University)
  • Published : 2015.01.06

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Aim and Objectives: This study investigated substitutions in the ATP synthase subunit 6 gene of mitochondrial DNA (mtDNA) as a potential diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Based on mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, approximately 465 bp of the ATP synthase subunit 6 gene were amplified and sequenced. Results: The sequencing revealed thirty-one mutations at 14 locations in ATP synthase subunit 6 of mtDNA in the ALL subjects. All were identified as single nucleotide polymorphisms (SNPs) with a homoplasmic pattern. The mutations were distributed between males and females. Novel haplotypes were identified in this investigation: haplotype (G) was recorded in 34% in diagnosed subjects; the second haplotype was (C) with frequency of 13% in ALL subjects. Neither of these were observed in control samples. Conclusions: These haplotypes were identified for the first time in acute lymphoblastic leukemia patients. Five mutations able to change amino acid synthesis for the ATP synthase subunit 6 were associated with acute lymphoblastic leukemia. This investigation could be used to provide an overview of incidence frequency of acute lyphoblastic leukemia (ALL) in Saudi patients based on molecular events.

Keywords

Acute lymphoblastic leukemia;ATP synthase subunit 6 gene;mtDNA;biomarker

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