Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML.
Salvatore Nicola BertuccioLaura AnselmiRiccardo MasettiAnnalisa LonettiSara CerasiSara PolidoriSalvatore SerravalleAndrea PessionPublished in: Cancers (2021)
Despite improvements in therapeutic protocols and in risk stratification, acute myeloid leukemia (AML) remains the leading cause of childhood leukemic mortality. Indeed, the overall survival accounts for ~70% but still ~30% of pediatric patients experience relapse, with poor response to conventional chemotherapy. Thus, there is an urgent need to improve diagnosis and treatment efficacy prediction in the context of this disease. Nowadays, in the era of high throughput techniques, AML has emerged as an extremely heterogeneous disease from a genetic point of view. Different subclones characterized by specific molecular profiles display different degrees of susceptibility to conventional treatments. In this review, we describe in detail this genetic heterogeneity of pediatric AML and how it is linked to relapse in terms of clonal evolution. We highlight some innovative tools to characterize minor subclones that could help to enhance diagnosis and a preclinical model suitable for drugs screening. The final ambition of research is represented by targeted therapy, which could improve the prognosis of pediatric AML patients, as well as to limit the side toxicity of current treatments.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- high throughput
- free survival
- end stage renal disease
- ejection fraction
- newly diagnosed
- single cell
- genome wide
- oxidative stress
- squamous cell carcinoma
- coronary artery disease
- cardiovascular events
- cardiovascular disease
- risk factors
- young adults
- single molecule
- cell therapy
- drug induced