Grants - V Scholar Grants - California - 2017

Ling Li, Ph.D.

Each year, around 10,000 patients with Acute Myeloid Leukemia (AML) in the US will die from the disease. About a quarter of AML patients have a particular change in the FLT3 gene. This change leads to a lower chance of surviving the disease. This genetic change causes a FLT3 protein to be defective. Drugs such as tyrosine kinase inhibitors (TKIs) are used to treat the effects of abnormal FLT3 protein (FLT3-ITD). However, they are not very effective.

A particular type of cancer cells called leukemia stem cells (LSCs) is not removed by drugs like TKIs. Researchers think LSCs are responsible for the disease coming back in people with AML. Thus, LSCs with FLT3-ITD are considered responsible for resistance to TKI treatment. Understanding why LSCs are resistant to TKIs will allow us to target these stem cells, and possibly cure people.

FLT3-ITD signals can be changed by modifying the protein in different ways such as methylation. Our studies found a link between methylation of FLT3-ITD and LSC resistance to TKI treatment. Thus, we think that FLT3-ITD methylation helps these stem cells resist drug treatment. We want to understand better how methylation helps LSCs survive. Also, we will test whether a lower amount of methylated FLT3-ITD protein leads to fewer cancer stem cells in test animals. Targeting protein methylation could lead to new ways to treat people with FLT3-ITD leukemia.