Novel Mutations in the Displacement Loop of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia: A Genetic Sequencing Study

Abstract

<b>Background:</b> Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children andrepresents approximately 25% of cancer diagnoses among those younger than 15 years of age. Materials and<br/><b>Methods</b>: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA(mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblasticleukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of thed-loop region were amplified and successfully sequenced. <br/><b>Results</b>: This revealed 132 mutations at 25 positionsin this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were allidentified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles wereobserved in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loopregion of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop ofmtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions(19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. <br/><b>Conclusions</b>:Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acutelymphoblastic leukemia is recommended.