By Oliver Worsley
|NYU's Susan Schwab|
Dr. Susan Schwab and her lab at the NYU Langone Medical Center have associated CXCR4 signaling as a positive regulator of T-cell acute lymphoblastic leukemia (T-ALL) growth and disease progression.
T-ALL is an aggressive type of blood cancer in which up to one in 5 children with the disease relapse within 10 years. Schwab describes it as "a particularly devastating cancer" due to the absence of treatment currently available.
In experiments using mice and human cells, the researchers found that they could halt the progression of T-ALL in bone marrow and spleen tissue within two weeks. They did this by blocking CXCR4--a receptor protein that targets T cells--helping T cells to mature and attract blood cells to the bone marrow, worsening the disease manifestation. Furthermore, they showed that they could slow disease progression in mice genetically engineered to develop T-ALL by inhibiting CXCL12--the major protein CXCR4 binds to.
"Our experiments showed that blocking CXCR4 decimated leukemia cells," says Schwab. Moving forward, her lab plans to develop more potent CXCR4 antagonists that can be used alongside the mainstay chemotherapy drugs used in the clinic.
Although CXCR4 inhibition in T-ALL patients hasn't been done yet, using CXCR4 inhibitors to disrupt the microenvironment of leukemia cells is under early investigation in other forms of leukemia and so far has been well tolerated.
As part of a new collaborative effort with a senior member of the Perlmutter Cancer Center, Ioannis Aifantis, they're working on the CXCR4-CXCL12 signaling complex and are hoping to understand T-ALL disease progression in greater detail.
- here's the release