Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13)

Recently, we and others reported a recurrent t(7;12)(q36;p13) found in myel oid malignancies in children less than or equal to 18 months of age and ass ociated with a poor prognosis. Fluorescence in situ hybridization studies m apped the 12013 breakpoint to the first intron of ETV6 and narrowed down th e region of 7036 involved, By using the sequences made public recently by t he Human Genome Project, two candidate genes in 7q36 were identified: the h omeobox gene HLXB9 and c7orf3, a gene with unknown function, Reverse transc ription-PCR of two cases with t(7;12), using primers for c70rf3 and ETV6, w as negative. However, reverse transcription-PCR for HLXB9-ETV6 demonstrated alternative splicing; the two major bands corresponded to fusion of exon 1 of HLXB9 to exons 2 and 3, respectively, of ETV6, The reciprocal ETV6-HLXB 9 transcript was not detected. It remains to be elucidated if the leukemic phenotype is attributable to the formation of the HLXB9-ETV6 fusion protein , which includes the helix-loop-helix and E26 transformation-specific DNA b inding domains of ETV6 or to the disruption of the normal ETV6 protein.