Mitochondrial D‐loop variations in paediatric acute myeloid leukaemia: a potential prognostic marker

Summary The D‐Loop region of mitochondrial DNA (mtDNA) is the regulatory region for its replication and transcription. There are two hypervariable regions (HV‐I, HV‐II) and the rate of mutation in these regions is 100‐ to 200‐fold that of nuclear DNA. In the current study, the entire D‐loop region of mtDNA was amplified in two overlapping polymerase chain reaction fragments and variations were evaluated in 44 paediatric acute myeloid leukaemia (AML) patients by direct DNA sequencing methods. Median age of the patients was 8·5 years (1–18 years) and the male:female ratio was 3·8:1. A total of 222 variations were observed at 118 positions in the D‐Loop of 35/44 (79·5%) AML patients. The most common variations were T→C (24·6%) and C→T (21·4%) followed by A→G (15·8%). There was no significant difference in the event‐free survival (EFS) of patients with or without any variations ( P = 0·40). Three variations in HV‐I, namely 16126T→C ( P = 0·05), 16224T→C ( P < 0·01) and 16311T→C ( P < 0·001), were significantly associated with inferior EFS. In conclusion, this is the largest study to show a high frequency of mtDNA variations in paediatric AML and their potential relevance as a prognostic marker in this disease.