April 2013 Newsletter

Leukemic Cells Demonstrate Gene Expression Profiles that May Confer Survival Advantage in the Post-Allogeneic Hematopoietic Stem Cell Transplant Environment

Thomas Fountaine, M.D., has pursued a project entitled “Leukemic Cells Demonstrate Gene Expression Profiles that May Confer Survival Advantage in the Post-Allogeneic Hematopoietic Stem Cell Transplant Environment.” His mentors are Jeffrey R. Andolina, M.D., M.S.  and Craig Mullen, M.D., Ph.D. in the Division of Pediatric Hematology/Oncology. Dr. Fountaine’s primary aim was to investigate whether acute lymphoblastic leukemia (ALL) cells adapt to the environment in ways that may promote cell survival ultimately leading to relapse and treatment failure. Doing this will help oncologists better understand why ALL in particular has a poor graft-vs.-leukemia (GvL) effect in the post-allogeneic transplant environment. Dr. Fountaine and his mentors generated mixed-lymphocyte reactions in vitro to identify cytokines of interest that dominate the post-Allo transplant environment and then exposed 5-human ALL cell lines to cytokines and cyclosporine (an important drug in human stem cell transplantation). They isolated RNA and performed RNA-sequencing analysis which generated a primary list of RNA-transcripts. They then used a combined multi-analytic approach and selected genes that were over-expressed by >2-fold-difference and had a p-value of < 0.05. A total of 59-genes satisfied the criteria. Functional pathway analysis was performed using a combination of DAVID (NIAIDH) and Ingenuity Pathway Analysis (IPA). Among the individual genes that were up-regulated, the following were of interest based on biological significance: (a) HLA-A, -B, -C, -E, and –H; (b) STAT-1; (c) GPB3; and (d) B2M. These genes and the pathways in which their gene products are involved suggest that the leukemia cells are evading the allogeneic-immune-based GvL effect through altered cell signaling and escape of immune surveillance.