Genomic profiling of acute myeloid leukaemia associated with ataxia telangiectasia identifies a complex karyotype with wild-type TP53 and mutant KRAS, G3BP1 and IL7R.

Abstract

Ataxia Telangiectasia (A-T) is an autosomal recessive disease, characterised by progressive neurodegeneration with cerebellar ataxia, oculo-cutaneous telangiectasia, immunodeficiency and cancer predisposition. It is caused by biallelic mutations in ATM (Ataxia Telangiectasia Mutated, chromosome 11q22.3) encoding a serine/threonine kinase essential in cell cycle control, DNA double-strand break repair and haematopoietic stem cell maintenance 1,2. Individuals with A-T classically develop lymphoid malignancies, a broad spectrum of other malignancies 3 and rarely, acute myeloid leukaemia (AML) 4-7. Previous AT-AML reports have described the karyotype and dismall clinical course (Supplementray Table S1). We performed sequential sample genomic profiling of an AML that developed in a 17-year-old female with A-T, to identify secondary genetic events towards myeloid malignancy (full clinical case history in Supplementary Information).