The evolution and history of Vinca alkaloids: From the Big Bang to the treatment of pediatric acute leukemia
Abstract
An attractive flower from the island of Madagascar has helped save the lives of thousands of children with acute lymphoblastic leukemia (ALL). Random mutations and alterations in the genome have led to the evolution of genes encoding enzymes that provide the periwinkle flower with an arsenal of secondary metabolites to thrive within the Madagascar ecosystem. Among the over 200 alkaloid compounds synthesized by the periwinkle, vincristine and vinblastine are the two most well-known for use in chemotherapy treatments, including for children with ALL. The complexities of the multi-step biosynthesis of vincristine and vinblastine, which have taken years to decode, highlight the importance of protecting the vast biodiversity on Earth, as other natural products that can save lives await discovery. This review addresses the discovery of vincristine and vinblastine, as well as the history of their existence in nature.
KEYWORDS
acute lymphoblastic leukemia, vincristine, vinblastine
Introduction
Ever since the genesis of our universe, change has been a constant theme in the cosmos, marked by endless cycles of creation, destruction, and rebirth. During this time, life somehow arose on at least one rocky, blue-green planet in the outer arm of a spiral galaxy among billions of others. The life that emerged on this planet is vast and varied, undergoing evolutionary cycles for eons. It is no surprise that the organisms here often acquire ailments and diseases that affect their ability to survive. For humans, it is disheartening when this unfortunate outcome befalls their children. One such condition is the diagnosis of pediatric leukemia. Although we now have treatment options that offer the possibility of real cures, it has taken decades of dedicated research to reach this important milestone. This review addresses one of these early treatments for leukemia, as well as the history and evolution of its existence.
