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New subtypes of oncogenic deregulation in childhood T-ALL

Presented By
Dr Petri Pölönen, St. Jude Children's Research Hospital, TN, USA
EHA 2022
Large-scale whole-genome sequencing, whole-exome sequencing, and RNA-expression profiling uncover new subtypes of T-cell acute lymphoblastic leukaemia (T-ALL). T-ALL represents approximately 15% of all newly diagnosed ALL cases in paediatric patients. T-ALL is an aggressive malignancy showing immunophenotypic diversity, including early T-cell precursor lymphoblastic leukaemia (ETP-ALL) and leukaemia of transformed thymocytes. About 20% of patients relapse or have refractory disease. Prognostic factors other than minimal residual disease are unclear [1]. Previous genetic research on patients with T-ALL identified 8 molecular subtypes with 106 putative drivers based on gene expression clustering [2]. However, this study had a limited cohort size, excluded refractory disease, and focused on alterations in coding parts of the genome. It is now known that T-ALL gene activation is also frequently achieved by alterations in non-coding parts of the genome, e.g.

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