Rachel Bergerson

E-mail: sapl0005@umn.edu

Thesis Advisor: David Largaespada

Year entered: 2003

Degrees received:
B.A., Biology, Augustana College, Rock Island, IL 2003

Honors and Awards:

• Golden Pipetman Award Fall 2005
• Cancer Biology Training Grant Fellowship 2005-2006
• Travel award for Top Poster and Presentation: Seventh International Workshop on Molecular Aspects of Myeloid Stem Cell Development and Leukemia; Annapolis, MD May 2007

Thesis research:
Mice carrying the Mll-AF9 fusion oncogene develop acute myeloid leukemia (AML), the phenotype observed in human patients with the t(9;11) MLL-AF9 translocation, but only after a long latency. We hypothesized that infection with a recombinant Murine Leukemia Virus (MuLV) could cooperate with MLL-AF9 expression to accelerate the onset of leukemia by causing the secondary mutations required for cancer progression. Wild-type or Mll-AF9 mice were injected with either MuLV (N=211) or were mock infected (N=68). MuLV-infected Mll-AF9 mice succumbed to leukemia more rapidly than all controls (P < 0.0001). MuLV proviral insertion sites were cloned from leukemia samples to identify the genes frequently mutated in Mll-AF9 positive leukemia. We studied the genes around these proviral insertions for aberrant expression in leukemic tissues. There was elevated expression of Mn1, a trend towards increased expression of Bcl11a and Fosb, and a trend towards decreased expression of Cd47 in our Mll-AF9 murine leukemia samples with nearby proviral insertions. There was also decreased expression of CD47 in tumor material from humans with AML harboring MLL-AF9 gene translocations. These genes may define genetic pathways that are altered during progression of leukemia induced by MLL fusion oncogenes.

Publications:

• Ohlfest JR, Demorest ZL, Motooka Y, Vengco I, Oh S, Chen E, Scappaticci FA, Saplis RJ, Ekker SC, Low WC, Freese AB, Largaespada DA. 2005. Combinatorial antiangiogenic gene therapy by nonviral gene transfer using the sleeping beauty transposon causes tumor regression and improves survival in mice bearing intracranial human glioblastoma. Mol. Ther. 12(5):778-88.
• Bergerson RJ, and Largaespada DA. Comment on Sauvageau et al, page 790: What gene have I ID'ed? Blood, 15 January 2008, 111(2): 471-472.
• Rachel J. Bergerson, Lara S. Collier, Sanne Lugthart, Raha Allaei, Susan K. Rathe, Baolin Wu, Rod A. Staggs, Kevin A.T. Silverstein, Keiko Akagi, Anne-Francoise J. Lamblin, Linda Wolff, John H. Kersey, Rudd Delwel, Scott C. Kogan, David J. Adams, and David A. Largaespada. An insertional mutagenesis screen for genes that cooperate with Mll-AF9 in leukemogenesis. Submitted to Blood, May 2008