The Role of S100A8/A9-IL6R in B-ALL Chemoresistance

Dr. William Carroll, M.D. – New York University Grossman School of Medicine, New York, NY 

In spite of dramatic improvements in outcome for B acute lymphoblastic leukemia (B-ALL) it remains a leading cause of cancer associated death in children and treatment is associated with short and long-term side effects. In an effort to understand how B-ALL cells evade therapy and result in relapse, we have studied genetic and epigenetic differences between blasts at diagnosis (sensitive) and relapse (resistant). Our work and results from others have identified key pathways that leukemia cells use to overcome treatment. Targeting these pathways will lead to more effective and potentially less toxic forms of treatment. We now have significant preliminary data showing that a majority of relapsed B-ALL cells express an inflammatory signature with overexpression of S100A8/A9 and IL6R that results in a protective niche within the bone marrow. The availability of agents already in clinical trials that block these pathways highlights the immediate clinical significance of this work.