  Chromosomal aberrations are very frequent in leukemias and several recurring
mutations capable of malignant transformation have been described. These
mutations usually occur in hematopoietic stem cells (HSC), transforming them
into leukemia stem cells. NUP98 gene translocations are an example of such
chromosomal aberrations; these translocations produce a fusion protein
containing the N-terminal portion of Nup98 and the C-terminal of a fusion
partner. Over 75% of Nup98 fusions can interact with chromatin, and lead to
changes in gene expression. Therefore, I hypothesize that nup98 fusions act as
rogue transcriptional regulators in the cell. Collecting previously published
gene expression data (microarray) from HSCs expressing Nup98 fusions, we can
generate data to corroborate this hypothesis. Several different fusions affect
the expression of similar genes; these are involved in a few biological
processes in the cell: embryonic development, immune system formation and
chromatin organization. Deregulated genes also present similar transcription
factor binding sites in their regulatory regions. These putative regulatory
transcription factors are highly interconnected through protein-protein
interactions and transcriptional regulation among themselves, and they have
important roles in cell cycle regulation, embryonic development, hematopoiesis,
apoptosis and chromatin modification.
