Current diagnosis and treatment for pediatric acute myeloid leukemia

Acute myeloid leukemia (AML) is a complex disease caused by chromosomal aberrations, mutations, epigenetic modifications, and the deregulated expression of genes, leading to increased myeloid cell proliferation and decreased hematopoietic progenitor cell differentiation. Although most of these aberrations are correlated with prognosis, accurate risk stratification remains a challenge even after incorporating these molecular markers. Currently, some genetic mutations that allow risk stratification have been identified in adult AML, including DNMT3A and IDH1/2. However, these mutations are rare in pediatric AML cases, indicating that a different pathogenesis may exist between adult and pediatric AML. To reveal further details of pediatric AML pathogenesis, the authors performed whole-exome sequencing and whole-transcriptome analysis using massively parallel sequencing technologies in addition to gene expression array. We found that PRDM16 and EVI1-overexpressing patients had significantly worse overall survival and event-free survival, and these overexpressed genes were useful for stratifying patients with FLT3-ITD positive and/or normal karyotype. In order to further this work and establish more appropriate risk classification and molecular target drug development, target validation clinical studies are needed and expected.