Coduplication of the FLT3 and MLL Genes in Pediatric Acute Myeloid Leukemia

Abstract

Tandem duplication (TD) of the FLT3 gene has recently been reported in pediatric acute myeloid leukemia (AML) and in adult AML and myelodysplastic syndrome (MDS). The TD of the MLL gene was also reported in adult AML. The TD of these 2 genes was found to be associated with a poor prognosis. To clarify the role of TD of these genes, we examined whether TD of the FLT3 and MLL genes developed simultaneously. We analyzed TD of the MLL gene in 7 pediatric patients who had TD of the FLT3 gene by reverse transcriptase-polymerase chain reaction (RT-PCR). Our study revealed that one of 7 patients had TD of both the FLT3 and the MLL genes. The patient with the TD of both genes died earlier than the other 6. This is our first pediatric patient with TD of the MLL gene. The mechanisms of TD of both genes are different because TD of the FLT3 gene was considered to be caused by nonhomologous recombination, and TD of the MLL gene by homologous recombination. However, because very rare TD of the MLL and FLT3 genes developed in a single patient suggests that the development of the FLT3 gene and the MLL gene may be related to an unknown similar etiology, for example, genomic instability, in leukemia.