Title of the Research Project:
“Delineating the Role of Mitochondrial Dysregulation in Richter’s Transformation.”
Research Project Summary:
Richter’s transformation (RT) is a rare but aggressive progression of the cancer that occurs in a small subset of patients who have already been diagnosed with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Normally, CLL / SLL cells are slow-growing, which is what makes it chronic. RT occurs when these slow-growing CLL / SLL cells suddenly change into a much more aggressive, rapidly growing form of lymphoma. Limited understanding of metabolic aspects and driving mechanisms at the cellular level have hindered the development of effective therapies for RT. This pre-clinical study does not utilize human subjects. Instead, it will use advanced mouse models that are designed to mimic RT in humans. By closely studying how the chemical pathways in a controlled laboratory environment work, Dr. Iyer hopes to better understand how RT cells replicate and grow out of control in these mice models to uncover key mechanisms that drive disease progression and potentially identify targets for new treatment regimens.
About the Award Recipient, Dr. Prajish Iyer:
Prajish Iyer, PhD, is currently a Staff Scientist in the Department of Systems Biology at City of Hope in Duarte, California. He was awarded his PhD in life sciences from Tata Memorial Cancer Centre, Advanced Center for Treatment Research and Education in Cancer (ACTREC) in India. Dr. Iyer moved to the United States for his postdoctoral fellowship at City of Hope, where he was soon promoted to staff scientist and joined the laboratory of Lili Wang, MD, PhD. His area of research focus has been to understand the molecular mechanisms of genetic alterations in CLL / SLL and to better understand changes that occur at the cellular level in those whose cancer progresses to RT.
Why Is Research About Mitochondrial Dysregulation in Richter’s Transformation Needed?
Mitochondria are parts within a cell that serve as the powerhouse that provides the energy for everything to run smoothly. But in RT cells, the mitochondria abnormally mutate and stop working correctly. When the mitochondria change and adapt, it allows the cancerous cells to have a survival advantage and replicate abnormally. By understanding exactly how the shift in energy takes place within the mitochondria, Dr. Iyer hopes to then be able to find ways to make it more difficult for these cells to survive and spread out of control by blocking certain survival pathways within the cells. Targeting these identified survival pathways within the mitochondria could be a promising strategy for disrupting the very foundation of RT cell survival by limiting the ability of the cancerous CLL / SLL cells to adapt and grow.
When Researching Richter’s Transformation, What Are the Challenges?
There are many challenges researchers face when studying RT. One of the biggest challenges is the general lack of in-depth knowledge, especially when it comes to understanding the genetic and metabolic pathways that lead to the development of the disease. It is also very difficult to obtain patient samples due to the rare occurrence of RT, which hinders the ability to perform comprehensive research studies and analyses. A significant challenge in laboratory research is the scarcity of pre-clinical mouse models for testing because developing these models is both time-consuming and expensive. Complicating things further is the differences that exist in the characteristics of the disease when patients are diagnosed, resulting in ability to pinpoint certain causes more complex.
How Will the Findings Be Used?
A poor prognosis is associated with RT, which underscores the urgency of research efforts to unravel the mechanisms driving this aggressive progression of the disease so that effective treatment strategies can be developed. While RT is rare, it is a devastating event when it does occur because most patients do not survive more than a year beyond diagnosis. The disease is often resistant to current treatment regimens used to treat CLL / SLL, highlighting the urgent need to find treatment approaches that will ultimately improve outcomes. Inhibiting key enzymes in RT cells shows promise in slowing down growth, offering a potential avenue for the development of new innovative treatments. Dr. Iyer’s focus on understanding the biological processes involved will hopefully lay the groundwork for future development of new treatment options that will effectively target this aggressive form of cancer and bring hope to those battling RT.
Please watch the interview between CLL Society’s Director of Scientific Affairs and Research, Robyn Brumble, RN, MSN and Prajish Iyer, PhD.
What Is the Goal of CLL Society’s Young Investigator Award?
This research award is intended to foster the academic career development of scientists who are either young in their careers or have not yet fully established themselves as independent researchers. The Young Investigator Award encourages the next generation of scientific leaders to perform research that is specific to CLL / SLL.
CLL Society invites you to read more about CLL Society’s Research Program. The 2024 Young Investigator Award was made possible through generous donations from those in our community who help us fund this important work. CLL Society is one of the only blood cancer organizations in the United States whose Research Program is dedicated solely to funding CLL / SLL research.
