Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma
A new publication in Blood (2016 Sep 29;128(13):1735-44,
Primary Author: Niels Weinhold, M.D., Assistant Professor
Despite the introduction of novel agents, relapse remains a challenge in the treatment of multiple myeloma. Understanding the underlying molecular mechanisms of myeloma growth and relapse following dose-intense chemotherapy could lead to new avenues of therapy aimed at overcoming these mechanisms. Dr. Gareth Morgan, Myeloma Institute director, and his research team performed the first longitudinal study that addressed the impact of a specific treatment. (A longitudinal study is an observational research method in which data is gathered for the same subjects repeatedly over a period of time; in this study at enrollment into a total therapy clinical trial and at relapse.) Investigating gene expression, chromosomal and mutation profiles, Morgan’s team identified activation of oncogenes and complete inactivation of tumor suppressor genes, as well as Darwinian-style evolutionary processes, as important contributors to myeloma cell death resistance. The study emphasizes the benefit of using alternate therapies with different action mechanisms to induce myeloma cell death and prevent relapse, especially in high risk patients with an inactivated TP53 gene.