Sam Milanovich, MD, Lab
Primary Research Focus
Sam Milanovich, MD, and his lab’s team focus on studying the genetic and epigenetic regulation of normal blood cell development and how mutations on these processes lead to leukemic transformation. The goal is to define mechanisms that lead to the formation of leukemia stem cells.
Defining critical oncogenic molecular mechanisms and pathways in leukemia stem cells will improve understanding of leukemogenesis, and why some patients are cured by conventional therapies while others relapse. These understandings will help Dr. Milanovich’s team to identify distinct subsets of patients who may benefit from different therapeutic approaches.
This information can ultimately be used when designing novel therapies to specifically target leukemia stem cells while limiting toxicities to normal blood development, ultimately improving outcomes for pediatric leukemia patients.
Behind the Research
Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) comprise the most common childhood cancers. Despite recent advances in therapy, acute leukemia remains a major cause of pediatric morbidity and mortality. Leukemia arises when normally developing hematopoietic precursors acquire leukemogenic mutations that transform them from normal hematopoietic stem cells or progenitors into leukemia stem cells.
Leukemia stem cells generate a heterogeneous, genetically diverse population of tumor cells that make up the bulk of the clinically detected, disease-causing tumor. These stem cells are characterized by unlimited self-renewal and have many biological differences from the bulk (non-stem cell) leukemia cells. These differences may cause leukemia stem cells to be more resistant to chemotherapy than the bulk tumor cells. Resistance of leukemia stem cells to conventional treatment explains why many cancers relapse months or years after therapy initially appears to have eradicated all detectable disease.
The Milanovich Lab utilizes a variety of methods to study molecular genetics in leukemia patient samples, leukemia cell lines and mouse models of normal blood and leukemia development.