Studying the clonal dynamics and evolution of leukemia using molecular barcodes
When we give a cancer a name we imply that it is a homogeneous entity. It is well known, however, that by the time cancer reaches a size to become clinically detectable it is a complex and large heterogeneous mixture of cancer cells. It is likely that this underlying heterogeneity plays an important role in both the development of the cancer and its response to treatment.
For example, a heterogeneous cancer may have small sub-populations of cells that are not the primary cells in maintaining the cancer but are relatively resistant to treatment and thus critical for its recurrence. A key aspect to understanding this heterogeneity is to be able to track the fate of a large number of cells simultaneously.
The goal of this proposal is to use an innovative cell tracking system that leverages the recent powerful advances in sequencing technology to track tens of thousands of cells and their progeny simultaneously. We will apply this system to better understand the development and chemotherapy resistance in a mouse model of acute myelogenous leukemia caused by a rearrangement in the MLL gene and to better understanding the dynamics and chemotherapy resistance in primary human leukemia cells. We believe that by better understanding the heterogeneity of human cancers that we can design better therapies for pediatric cancers, such as leukemia, such that fewer patients succumb to these awful diseases.