A direct comparison, and prioritisation, of the antigens ex-pressed in adult and paediatric acute myeloid leukaemia: a systematic review and meta-analysis

Acute Myeloid Leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60-75% but fall to 5-15% in older AML patients. This systematic review aims to determine whether the altered genes affect the same molecular pathways and genes, indifferent of patient age and therefore whether AML patients could benefit from the repurposing drugs across age boundaries. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles and 71 targets for therapy for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then prioritised the antigens according to their potential to act as targets for the immunotherapy of AML and found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analysis were performed on the 20 highest scoring targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focussed on ways to target the highest scoring antigens such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful.