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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 741-747
NUP98 Is Fused to PMX1 Homeobox Gene in Human Acute
Myelogenous Leukemia With Chromosome Translocation t(1;11)(q23;p15)
Takuro Nakamura,
Yukari Yamazaki,
Yoshiaki Hatano, and
Ikuo Miura
From PRESTO, Japan Science and Technology Corp, Tokyo, Japan; The
Cancer Institute, Japanese Foundation for Cancer Research, Tokyo,
Japan; and the Third Department of Internal Medicine, Akita University
School of Medicine, Akita, Japan.
The nucleoporin gene NUP98 was found fused to the
HOXA9, HOXD13, or DDX10 genes in human acute
myelogenous leukemia (AML) with chromosome translocations
t(7;11)(p15;p15), t(2;11)(q35;p15), or inv(11)(p15;q22), respectively.
We report here the fusion between the NUP98 gene and another
homeobox gene PMX1 in a case of human AML with a
t(1;11)(q23;p15) translocation. The chimeric NUP98-PMX1 transcript was detected; however, there was no reciprocal
PMX1-NUP98 fusion transcript. Like the NUP98-HOXA9
fusion, NUP98 and PMX1 were fused in frame
and the N-terminal GLFG-rich docking region of the NUP98 and
the PMX1 homeodomain were conserved in the NUP98-PMX1 fusion,
suggesting that PMX1 homeodomain expression is upregulated and that the
fusion protein may act as an oncogenic transcription factor. The fusion
to NUP98 results in the addition of the strong transcriptional
activation domain located in the N-terminal region of NUP98 to PMX1.
These findings suggest that constitutive expression and alteration of
the transcriptional activity of the PMX1 homeodomain protein may be
critical for myeloid leukemogenesis.
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