Session 1B Lectures by Fellows/Associates

Acute promyelocytic leukemia: A bench to bedside journey

My area of research is centered on acute leukemia’s. There remain significant challenges in diagnosis, accurate prognostication and management of these conditions. Additionally, there are specific challenges in delivery of cost effective care in India and many parts of the developing world. A major problem in the management of acute leukemia is the high recurrence rate, especially in adults and the elderly. While there has been a significant increase in the understanding of the biology of these malignancies the reasons for recurrence in spite of conventional therapy is not clear in most cases. More research is required to address the reasons and also ability to accurately predict relapse of acute leukemia. One area of special interest to our group is the role played by the micro-environment in the bone marrow in which these malignant cells reside in inducing resistance to therapy. Preliminary work by our group and others suggest that there is significant survival advantage and drug resistance to conventional therapy mediated by cells in the bone marrow microenvironment. Our preliminary data suggests that this phenomenon is seen in all types of leukemia’s though it would appear that the major mediators and pathways are different in different in subtypes of leukemia. We have made significant progress in understanding the mechanism of microenvironment mediated drug resistance to arsenic trioxide in acute promyelocytic leukemia (APL). In a recent publication from our group we have suggested a strategy in APL to overcome such resistance, which we went onto translate into a clinical trial. We hope that we will be able to identify similar strategies to overcome microenvironment mediated drug resistance to chemotherapeutic agents in other subtypes of acute leukemia. We feel this information along with additional work that we do in evaluating mechanisms of drug resistance will help direct our research on the use of novel agents and novel combinations of therapy to overcome such drug resistance in leukemia.