Chromosomal instability is poorly defined and used inconsistently and imprecisely. It is the increased propensity to chromosome aberrations due to chromosome replication, repair, or segregation. Therefore, acquired genetic changes are central to leukemia development. Fast-growing cells require substantive amount of energy; however, tumor cells take up more glucose, processing it through aerobic glycolysis producing large lactate amounts with lower use of oxidative phosphorylation to generate ATP. The Warburg effect is characterized by reduced use of tricarboxylic acid cycle, so pyruvate made in glycolysis is converted into lactate and expelled, but this metabolic pathway is energetically inefficient. When genes are malfunctioning, both oncogenes and tumor suppressor genes influence negatively the switch between aerobic glycolysis and extensive use of TCA cycle to generate ATP, as the normal gene replication and expression require adequate energy levels. Chromosomal instability is increasingly entangled and unnecessarily complex. So far, researchers focused solely on studying the mass and have forgotten the energy. The intrinsic property of melanin to transform light into chemical energy, through water dissociation, as chlorophyll in plants, opens a new landscape in chromosome biology, highlighting the role of the environment toxics in leukemia pathogenesis, inhalation being the dominant pathway of exposure.
Part of the book: Germ Line Mutations Associated Leukemia