Molecular dissection of a hyper-aggressive CBFB-MYH11/FLT3-ITD–positive acute myeloid leukemia

Abstract

AbstractAcute Myeloid Leukaemia (AML) is a haematological malignancy showing a hypervariable landscape of clinical outcomes and phenotypic differences, explainable by heterogeneity at the cellular and molecular level. Among the most common genomic alterations,CBFB-MYH11rearrangement andFLT3-ITD gene mutations, have opposite clinical significance and are unfrequently associated. We present here a Molecular Case Report in which these two events co-exist an ultra-aggressive phenotype resulting in death in 4 days from hospital admittance. Somatic and germline Whole Exome Sequencing analysis was performed to uncover other putative driver mutations, de-novo genomic structural events or germline clusters increasing cancer insurgence. Only three mutations inLTK,BCAS2andLGAS9were found, unlikely causative of the exhibited phenotype, prompting to additional investigation of the rareCBFB-MYH11/ FLT3-ITD scenario.