1. Jacquie Hirsch Leukemia Research Project Eunice S. Wang MD Norma J. Nowak PhD Roswell Park Cancer Institute

2. Leukemia is a cancer of the blood where normal blood cells have gone “bad”

3. DNA, Chromosomes, and genes For example, genes on X and Y chromosomes determine your gender. Each cell contains DNA DNA is the genetic code inherited from your parents DNA is arranged in structures called chromosomes (X-like). Each chromosome consists of thousands of genes Genes tell cells how to work. Genes

4. Patients with acute MLL+ leukemias have poor outcomes No MLL (80%) MLL gene (30-50%) Years after diagnosis Percentage of patients alive Without leukemia events

5. Goal of our Research The goal of this project is to identify and characterize the key genes and pathways involved in MLL-associated leukemia for future development of novel treatments for this specific acute leukemia type.

6. Gene/Genetic analyses

7. Gene expression data (33,000 genes per sample)

8. So… what does this data all mean????

10. Biological Network models A social network is a description of the social structure between actors, mostly individuals or organizations. It indicates the ways in which they are connected through various social familiarities ranging from casual acquaintance to close familiar bonds

11. 1. Altered Gene List 2. Human Reference Network 3. Cancer Specific Network 5. Evaluate Statistical Significance of Cancer Specific Network 4. Identify Network Modules Systems Biology Workflow

12. MLL-rearranged T-AML disease network Network of ≈500 genes < 20% genes associated with leukemia’s 35% novel genes 10 novel drug targets

13. MLL-rearranged T-AML disease subnetwork

14. Other funded research American Society of Hematology (2012) poster presentation -TH-302 in acute leukemia Krista Pundt (RPCI graduate student)

15. This work was made possible by: Jacquie Hirsch for ALL Foundation Special thanks to: Dancers Give Back