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Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 2118-2122
Acute Mixed Lineage Leukemia With an inv(8)(p11q13) Resulting in
Fusion of the Genes for MOZ and TIF2
Jian Liang,
Leonard Prouty,
B. Jill Williams,
Mark A. Dayton, and
Kerry L. Blanchard
From the Departments of Molecular Biology and Biochemistry,
Pediatrics, Urology, and Medicine, the Feist-Weiller Cancer Center,
Louisiana State University Medical School, Shreveport, LA.
Chromosomal abnormalities in acute leukemia have led to the
discovery of many genes involved in normal hematopoiesis and in malignant transformation. We have identified the fusion partners in an
inv(8)(p11q13) from a patient with acute mixed lineage leukemia. We
show by fluorescence in situ hybridization (FISH) analysis, Southern
blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR)
that the genes for MOZ, monocytic leukemia
zinc finger protein, and TIF2,
transcriptional intermediary factor 2, are involved in the inv(8)(p11q13). We demonstrate that the inversion
creates a fusion between the 5 end of MOZ mRNA and the
3 end of TIF2 mRNA maintaining the translational frame
of the protein. The predicted fusion protein contains the zinc finger domains, the nuclear localization domains, the histone
acetyltransferase (HAT) domain, and a portion of the acidic domain of
MOZ, coupled to the CREB-binding protein (CBP)
interaction domain and the activation domains of TIF2. The
breakpoint is distinct from the breakpoint in the t(8;16)(p11;p13)
translocation in acute monocytic leukemia with erythrophagocytosis that
fuses MOZ with CBP. The reciprocal TIF2-MOZ fusion gene is not expressed, perhaps as a
result of a deletion near the chromosome 8 centromere. The
MOZ-TIF2 fusion is one of a new family of chromosomal
rearrangements that associate HAT activity, transcriptional
coactivation, and acute leukemia.
© 1998 by The American Society of Hematology.
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