Recently, we and others reported a recurrent t(7;12)(q36;p13) found in
myeloid malignancies in children < or =18 months of age and associated
with a poor prognosis. Fluorescence in situ hybridization studies mapped
the 12p13 breakpoint to the first intron of ETV6 and narrowed down the
region of 7q36 involved. By using the sequences made public recently by
the Human Genome Project, two candidate genes in 7q36 were identified: the
homeobox gene HLXB9 and c7orf3, a gene with unknown function. Reverse
transcription-PCR of two cases with t(7;12), using primers for c7orf3 and
ETV6, was 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-HLXB9 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 binding domains of ETV6 or to the disruption
of the normal ETV6 protein