Figure 5.

Mitosis - segregating the blueprint for leukemia. During mitosis, the DNA and the cytoplasm of the cell have to be segregated to the daughter cells. The spindle assembly checkpoint (SAC) is a surveillance mechanisms which monitors interactions between chromosomes and microtubules and arrests cells at metaphase until every single chromosome has properly attached to the mitotic spindle. Restriction is achieved through inhibition of the activating APC/C-subunit Cdc20. Loss of function of SAC proteins such as BubR1, Mad2 or Bub1 (shown in green) reduces the accuracy of the SAC and favors chromosomal maldistribution. Overexpression of mitotic kinases such as Plk1, Aurora A and B (shown in red) can also result in premature anaphases. Small molecule inhibitors targeting Plk1 and the Aurora kinases are currently tested in clinical studies in AML patients (shown in yellow). See text for details.