Integrin mediated cellular adhesion may alter the cytokine profile in acute lymphoblastic leukemia

2015-07-09Although survival rates are promising in children with Acute Lymphoblastic Leukemia, in relapsed childhood ALL, survival rates remain a problem. More than 80% of first relapse of childhood and adult ALL occurs in the bone marrow. It has been shown that the bone marrow can promote cell adhesion mediated drug resistance (CAM‐DR) in leukemia cells by direct cell‐to‐cell interaction. The adhesion of ALL cells to the bone marrow stromal cells can also stimulate the secretion of soluble factors which leads to soluble factor mediated drug resistance (SFM-DR). A combination of these two forms of drug resistance is also possible. Previous studies indicate that by blocking leukemia integrin alpha4 and more recently alpha6 adhesion to their supportive bone marrow stroma environment, leukemia cells can be sensitized to chemotherapy. We hypothesized that SFM‐DR is also involved in this alpha6‐mediated drug resistance. Here, we show that there is a distinct cytokine profile involved in alpha6‐mediated drug resistance indicating that particular cytokines could play a role in chemoresistance as well. Taken together, this research attempts to understand the underlying mechanism of drug resistance in ALL that could lead to novel, more appropriately developed treatments