The evolution and history of Vinca alkaloids: From the Big Bang to the treatment of pediatric acute leukemia.

Jeffrey W Taub, Yubin Ge, Larry H Matherly, Steven A Buck, Ana C Xavier, Holly Edwards

Journal: Pediatric blood & cancer 2024;71(11):e31247

PMID: 39120434

Abstract

An attractive flower from the island of Madagascar has in part saved the lives of thousands of children with acute lymphoblastic leukemia (ALL). Random mutations and alterations to the genome led to the evolution of genes encoding enzymes, which would provide the periwinkle flower an arsenal of secondary metabolites to survive within the Madagascar ecosystem. Of the over 200 alkaloid compounds synthesized by the periwinkle, vincristine and vinblastine are the two most well-known being used for chemotherapy treatments, including for children with ALL. The complexities of the multi-step biosynthesis of vincristine and vinblastine, which has taken years to decode, highlight the importance of protecting the vast biodiversity on earth as other natural products that can save lives await to be discovered. This review addresses the discovery of vincristine and vinblastine, as well as the history of their existence, in nature.

© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.

Address: Division of Pediatric Hematology/Oncology, Children's Hospital of Michigan, Detroit, Michigan, USA.; Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, USA.; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.; Division of Pediatric Hematology/Oncology, Children's Hospital of Michigan, Detroit, Michigan, USA.; Division of Hematology/Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA.; Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA.

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