Scientists have shown that trichostatin A could be a potent apoptosis inducer to target chronic lymphocytic leukemia cells.
Chronic lymphocytic leukemia (CLL) is a cancer of white blood cells (leukocytes) in adults. In this type of cancer, functionally incompetent B cells grow out of control and tend to accumulate in the bone marrow and blood. These B cells are characterized by CD5+, CD19+ and CD23+ expression and are adept at disturbing the natural apoptosis pathway. The survival rate of patients with CLL varies widely, from about several months to more than 10 years, on the basis of the stage of disease. Typically, patients with a slow disease progression require only regular screening and infrequent therapeutic intervention, while patients with a rapid progression require immediate chemotherapy or even allogeneic stem cell transplantation.
In one of our previous blogs, we have talked about targeting CLL cells using engineered T cells, which are capable of expressing cell surface tumor-identifying killer receptors. Development of new treatment modalities along with the standard therapies are underway to cure CLL. These new options are important, since standard therapy sometimes elicits only a partial response or no response at all. Previously, studies have shown the involvement of the Wnt pathway in the development of several types of cancer. CLL cells also have shown a constitutionally active Wnt signaling pathway by overexpressing Wnt genes, in particular upregulation of pathway members such as Wnt3 and lymphoid enhancer-binding factor 1. Functionally, this results in increased resistance to apoptosis.
Recently, a group at University at Cologne, Germany, demonstrated that targeting the Wnt pathway may lead to new treatment choices for CLL therapeutics . They screened a Wnt compound library with 75 Wnt modulators against CLL and healthy peripheral blood mononuclear cells (PBMCs). They found trichostatin A to be an outstanding drug, specifically inducing apoptosis in CLL cells. Further, primary cells from patients who had critical mutations and already had undergone extensive previous treatments also responded well to the treatment. In addition, combining trichostatin A with the established CLL drugs fludarabine or bendamustine showed an additive effect in vitro. Taken together, trichostatin A appears to act via a dual anti-HDAC/Wnt mechanism with a high selectivity and efficacy in CLL and therefore warrants further investigation.
The above mentioned study has clearly demonstrated the remarkable effect of trichostatin A in primary cell culture derived from chronic lymphocytic leukemia patients. HemaCare is a leading provider of different cell types from healthy and patient donors. HemaCare supplies chronic lymphocytic leukemia cells obtained from volunteer donors, available for your research needs.
[1.] Peiffer L. et al., Trichostatin A effectively induces apoptosis in chronic lymphocytic leukemia cells via inhibition of Wnt signaling and histone deacetylation. J Cancer Res Clin Oncol (2014) 140:1283–1293