Translocations in Acute Leukemia
Professor of Biochemistry
Ingram Professor of Cancer Research
Assoc. Director for Basic Research
Vanderbilt-Ingram Cancer Center
Preston Research Building, Rm 512
One of the major focuses of our lab is the t(8;21), which is one of the most frequent chromosomal translocations in acute leukemia. The t(8;21) disrupts the functions of the RUNX1 DNA binding transcription factor and the MTG8 transcriptional co-repressor. The fusion of portions of these two genes at the chromosomal breakpoint, creates a chimeric gene that encodes a fusion protein that triggers leukemia. To understand how these translocation fusion proteins cause cancer, we must understand the normal regulatory roles of each of the normal genes (RUNX1 and MTG8) and then uncover how the fusion of parts of these two genes alters these functions to cause cancer. To uncover the physiological functions of Mtg8, we have constructed mice lacking this gene. The Mtg8-null mice shortly after birth, likely due to altered Wnt and Notch signaling and disrupted regulation of gene expression. Like its Drosophila homologue Nervy, Mtg8 is most highly expressed in the developing brain and spinal column. Our goal for this project is to define the neurological defects that lead to early perinatal lethality in these mice.