E-Selectin as a Biomarker in Acute Myeloid Leukemia

Brian Jonas, MD, PhD, associate professor of medicine at UC Davis Health in Sacramento, California, discusses e-selection as a biomarker in acute myeloid leukemia (AML), and how e-e-selectin inhibition works along with chemotherapy to decrease tumor growth.

According to Jonas, there is limited experience in targeting the tumor microenvironment in AML, but research suggests that it is a possibility. Specifically, a novel drug called uproleselan (GMI-1271) has been able to interact with the AML tumor microenvironment.

In a study, the addition of uproleselan to chemotherapy of mitoxantrone, etoposide, cytarabine led to high rates of remission in patients with relapsed or refractory AML. Moreover, the treatment was well-tolerated with low rates of induction mortality and mucositis. The results strongly support the need for future study of uproleselan in AML, in a randomized phase 3 fashion.

There is also rationale for additional study of e-selectin inhibition, which could pave the way for other therapies, according to Jonas.

Transcript:

0:07| [E-selectin] is involved in the expression of endothelial cells in the microvasculature of the bone marrow, and it’s involved in the maintenance of normal hematopoietic stem cells. However, the leukemia cells can co-opt the system. They can express the E-selectin ligand, which then gives them protection from chemotherapy and from the various bone marrow microenvironment–mediated protected pathways. It’s a way for them to enhance their own safety in a receptive microenvironment.

0:47 | That begs the question: Could this be a targetable situation? We don’t have much experience targeting the microenvironment in AML yet. What’s interesting about the development of uproleselan [is that it’s] a drug that targets the AML cells’ interaction with their microenvironment. The rationale is that if you inhibit this interaction between E-selectin and the E-selectin ligand on the leukemia cells, they lose that receptive microenvironment protection from chemotherapy and the receptive area that supports their growth.