FLT3 and NPM1 mutations in acute myeloid leukemia (AML) with double trisomy of chromosomes 8 and 21

Abstract

Aim Characterisation of AML by cytogenetics and molecular genetics. Patient history A 60-year-old female with previous melanoma and squamous cell carcinoma presented with 60% blasts in peripheral blood and > 70% blasts in bone marrow. Flow cytometry was positive for CD13, CD33, CD117 and HLA-DR, but lacked CD34 and aberrant CD7 expression. These results are consistent with AML. Methods Karyotyping, fluorescence in situ hybridisation (FISH) and mutation analysis of FLT3 and NPM1. Results and discussion A 48, XX,+ 8,+ 21 karyotype was found and FISH confirmed. NPM-1 was positive and FLT3-ITD mutant allele burden 31.7%. The significance of double trisomy 8 and 21 in AML with FLT3-ITD and NPM1 mutations is unclear. However, trisomy 8 or 21 as sole abnormalities is associated with intermediate to poor prognosis and adversely affected by age. NPM1 mutations usually have favourable outcome, however the poor prognosis of FLT3-ITD overrides NPM1 risk status. Overall these findings appear to indicate an unfavourable outcome.