PO-315 The mutational and transcriptome landscape of infant B-cell acute lymphoblastic leukaemia: the INTERFANT treatment protocol experience

IntroductionInfant B-cell precursor acute lymphoblastic leukaemia (iBCP-ALL) has dismal prognosis, especially with MLLgene rearrangements (MLLr) which are hallmark clonal leukemogenic drivers. Molecular pathogenesis of MLLr-iBCP-ALL remain somehow enigmatic and in vivo recreation of MLLriBCP-ALL is challenging.Material and methodsWe performed whole-genome, exome, targetted and RNA-sequencing on an Interfant study discovery cohort of 50 iBCP-ALLs (27MLL-AF4+, including relapses, 5MLL-AF9+and 10non-MLL). An independent validation cohort of 82iBCP-ALLs (43MLL-AF4+, 11MLL-AF9+, and 28non-MLL) was used for targeted DNA-sequencing/qRT-PCR.Results and discussionsiBCP-ALL shows an extremely low frequency of somatic mutations, irrespective of the presence/subtype of MLLr, with the predominant leukemic clone carrying a mean of 2.5 non-silent mutations. Recurrent mutations were exclusively found in KRAS and NRAS, which were more frequent in the MLL-AF4+than in MLL-AF9+/non-MLL iBCPALL due to common NRAS mutations found in MLL-AF4 +infants (32% vs 6%; p