Graduate student Bahareh Pezeshkian publishes in PLoS ONE

Leukemia is a cancer of the blood resulting in an abnormal increase of white blood cells. In the most common type of the disease, called Acute Myeloid Leukemia, causes the white blood cells to accumulate in the bone marrow, disrupting the production of red blood cells. Even after an initial chemotherapy leading to remission, in 80% of patients the disease reoccurs. Endothelial cells [ECs] line the inside surface of blood vessels. The laboratory of CBR member Gerard Madlambayan, of the Department of Biological Sciences, studies the interaction of endothelial cells with leukemia. Recently, Madlambayan’s group published a report in PLoS ONE (volume 8, article number e60823) titled Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanisms. In their introduction, they write that previous studies

“indicate an intimate relationship between ECs and leukemia, wherein leukemia cells are able to significantly alter EC activity. Given this response, we hypothesized that leukemia cells alter EC activity, and through this altered activity, ECs produce microenvironments responsible for leukemia growth, survival and, ultimately, relapse. In this paper, we describe the ability of leukemia cells to change the behavior of resting ECs by inducing the biological process of EC activation.”

Their conclusions have important implications for improving current chemotherapy techniques.

“In this study we demonstrate a novel mechanism wherein the inflammatory response of EC activation initiates activities that play a role in leukemia progression and relapse. We found that EC activation leads to increased leukemia cell adhesion to ECs resulting in leukemia cell quiescence and resistance to chemotherapy (Ara-C). Upon their release, leukemia cells re-enter cell cycle suggesting that this process may be involved in the high incidences of relapse. Preventing or inducing the release of adherent leukemia cells helps disrupt this protective environment, making more cells susceptible to chemotherapy, increasing overall leukemia cell killing and potentially eliminating the cellular components involved in relapse. These observations point to the importance of considering adjuvant therapies that aim to prevent this interaction and/or release already adherent leukemia cells as a way to augment the effects of current chemotherapy”

The lead author on the study is Bahareh Pezeshkian, a graduate student in the Biomedical Sciences: Biological Communication PhD program. Two of the coauthors, Kelley Tamburo and Christopher Donnelly, performed this research while undergraduates in Madlambayan’s lab. They both graduated with bachelor’s degrees in biology. Also contributing was Timothy Geddes of the Department of Radiation Oncology at William Beaumont Health System. PLoS ONE is an open access journal, so anyone can download and read this study without a subscription.