The RUNX1 gene is frequently rearranged in acute
leukemia. We cloned a novel RUNX1 chimeric gene generated by t(7;21)(q11.2;q22) in a patient with
acute myeloid leukemia. 3'-rapid amplification of
cDNA ends analysis showed a tail-to-tail fusion between RUNX1 on 21q22 and
DTX2 on 7q11.2, with an insertion of short complementary sequence from UPK3B adjacent to
DTX2.
DTX2 encodes a putative E3-ubiquitin
ligase with no known
biological function. There are two possible functions of RUNX1-reversed UPK3B-
DTX2: one from aberrant RUNX1 chimeric
protein and the other from the reversed sequence of
DTX2. The predicted aberrant
protein expressed under the RUNX1 promoter was highly structurally similar to RUNX1a. In a reporter assay, the aberrant
protein inhibited the trans-activation function of RUNX1 in a dominant-negative manner, similar to RUNX1a. In contrast, the
DTX2 reversed sequence may degrade wild-type
DTX2 transcript or suppress its translation. In conclusion, we identified a novel fusion RUNX1 partner,
DTX2, which chimerize in a reverse direction. This is the first example of RUNX1 chimera in an opposing direction generated by
chromosomal translocation in
leukemia. In addition to the aberrantly truncated
RUNX1 protein, the
DTX2 antisense sequence may play some role in the development of
leukemia carrying the t(7;21) translocation.