NUP98-HOXA9 AND AML

Project: Research project

Project Details

Description

DESCRIPTION: (adapted from the investigator's abstract) The t(7;11) in
patients with acute myeloid leukemia (AML) generates a fusion gene encoding
the amino-terminal NUP98, an FG repeat-containing nuclear pore complex
protein (NPC), and the carboxy-terminus of HOXA9, a homeotic transcription
factor. The NUP98 portion of NUP98-HOXA9 contains 37 of the 38 FG repeat
motif of NUP98. The HOXA9 part contains the HOXA9 DNA-binding domain and a
TRP-containing motif that mediates interactions between HOXA9 and other
transcription factors. The long term objective is to understand the exact
mechanism by which NUP98-HOXA9 contributes to leukemia. To achieve this
goal, the functionally critical motifs in the NUP98 and HOXA9 portions of
NUP98-HOXA9 that mediate its ability to transform NIH3T3 cell will be
defined, as will the proteins that interact with these motifs. The ability
of each NUP98-HOXA9 isoform to induce AML in vivo will be tested by
genetically engineering mice to express the chimeric proteins. Further,
these mice will be bred onto a BXH2 genetic background to identify mutations
that cooperate with NUP98-HOXA9 to induce AML. Finally, the normal in vivo
functions of NUP98 and HOXA9 will be studied by examining phenotypic effects
of loss- or gain-of-function mutations in mice. These studies should
further our understanding of the molecular mechanism of oncogenesis in an
expanding subgroup o AML patients with translocations that link nucleoporins
to nuclear proteins.
StatusFinished
Effective start/end date4/1/987/31/13

ASJC

  • Medicine(all)